24th June 2003 1 World Health Organization Clinical Staging, AIDS surveillance and Mortality in...

24th June 2003 1

World Health Organization

Clinical Staging, AIDS surveillance and Mortality in

resource-poor settings

a clinician’s view of strategic information needs

Clinical Staging, AIDS surveillance and Mortality in

resource-poor settings

a clinician’s view of strategic information needs

Charlie Gilks

Surveillance, Research Monitoring and EvaluationDepartment of HIV/AIDS

24th June 2003 2


Some core conceptsSome core concepts

HIV slowly destroys part of the immune system

Infected individuals pass through different stages

Advanced infection characterised by a few diseases

Death is the ultimate outcome for most

ARVs successfully modify the course of disease

We are in the “three by five” era

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24th June 2003 4


Mortality: resource-rich countries

Mortality: resource-rich countries

Universal registration of deaths Cause of death and predispositions included

AIDS-defining diseases (ADDs)

HIV often listed as predisposition electronic linkages with HIV databases comprehensive data with clear time trends counting deaths is a HUGE advocacy tool

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Annual number of reported HIV-related deaths, USA, 1991-2001Annual number of reported HIV-related deaths, USA, 1991-2001

0

10,000

20,000

30,000

40,000

50,000

60,000

Source: CDC Surveillance Reports, 1991-2001

Num

ber o

f HIV

-rela

ted

deat

hs

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Mortality: resource-poor countries

Mortality: resource-poor countries

Very little vital registration of deaths HIV or AIDS rarely included only data come form population-based studies much extrapolation from demographic data huge advocacy value of these estimates

BUT how can we capture changes with ART?An information gap - better sentinel surveillance

...

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AIDS SurveillanceAIDS Surveillance

The first Public Health response to the epidemic

The aim is to capture extent of HIV-related disease:- successful in high and some middle income counties- powerful advocacy tool - clear trends with time emerge- enables impact of ART to be seen quickly and clearly

AIDS (Acquired Immune Deficiency Syndrome) isnot a single disease entity but a surveillance definition

The CDC case definition has changed 3 times

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CDC case definition, 1993CDC case definition, 1993 Laboratory evidence of HIV infection; and CD4 cell count less than 200 cells/ mm³ or CD4 cells account

for fewer than 14 percent of all lymphocytes or Presence of one or more indicator diseases:

– Candidiasis of bronchi, trachea, or lungs;Candidiasis, esophagea;Cervical cancer, invasive;Coccidioidomycosis, disseminated or extrapulmonary; Cryptococcosis, extrapulmonary; Cryptosporidiosis, chronic intestinal (greater than 1 month's duration); Cytomegalovirus disease (other than liver, spleen, or nodes); Cytomegalovirus retinitis (with loss of vision); Encephalopathy, HIV-related;Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis; Histoplasmosis, disseminated or extrapulmonary; Isosporiasis, chronic intestinal (greater than 1 month's duration); Kaposi's sarcoma; Lymphoma, Burkitt's (or equivalent term); Lymphoma, immunoblastic (or equivalent term); Lymphoma, primary, of brain; Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary; Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary); Mycobacterium, other species or unidentified species, disseminated or extrapulmonary; Pneumocystis carinii pneumonia; Pneumonia, recurrent; Progressive multifocal leukoencephalopathy; Salmonella septicemia, recurrent; Toxoplasmosis of brain; Wasting syndrome due to HIV

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AIDS cases in the USAAIDS cases in the USA

0

20,000

40,000

60,000

80,000

100,000

120,000

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Numb

er of

report

ed AI

DS ca

ses

0

5

10

15

20

25

30

35

40

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001Source: CDC Surveillance Reports, 1991-2001

Repo

rted A

IDS c

ases p

er 100

,000 p

opula

tion

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European case definition, 1993European case definition, 1993

Same as CDC 1993 minus CD4 cell count

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WHO case definition for AIDS surveillance (Bangui)

WHO case definition for AIDS surveillance (Bangui)

At least 2 major signs in combination with at least 1 minor sign Major signs:

– Weight loss of at least 10% of body weight– Chronic diarrhoea for > 1 month– Prolonged fever for > 1 month

Minor signs: – Persistent cough for > 1 month– Generalized pruritic dermatitis– History of herpes zoster– Oropharyngeal candidiasis– Chronic progressive or disseminated herpes virus infection– Generalized lymphadenopathy

Or generalized KS or cryptococcal meningitis

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Expanded WHO case definition for AIDS surveillance (Abidjan)

Expanded WHO case definition for AIDS surveillance (Abidjan)

Laboratory evidence of HIV infection and One or more of following:

– 10% body weight loss or cachexia, with diarrhoea or fever, or both, intermittent or constant, for > 1 month; Cryptoccocal meningitis; pulmonary or extra-pulmonary TB; KS; Neurological impairment sufficient to prevent independent daily activities not known to be due to a condition unrelated to HIV infection; Candidiasis of the oesophagus; Clinically diagnosed life-threatening or recurrent episodes of pneumonia; invasive cervical cancer

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Revised Caracas/PAHO AIDS definition

Revised Caracas/PAHO AIDS definition

Laboratory evidence of HIV infection and Cumulative points assigned to following

conditions exceed 10 points:– KS (10); Disseminated/extrapulmonary/non-cavity pulmonary TB

(10);Oral candidiasis/hairy leukoplasia (5); Pulmonary TB with cavitation or unspecified (5); Herpes zoster in person of 60 years or less (5); central nervous system dysfunction (5); diarrhoea > 1 month (2); fever at least 38 for at least a month (2); cachexia or weight loss of more than 10% (2); asthenia of at least a month (2); persistent dermatitis (2); anaemia, lymphopenia, and/or thrombocytopenia (2); persistent cough or any pneumonia, and/or thrombocytopenia (2); lymphadenopathy of at least 1 cm at at least two non-inguinal sites (2) (number of points in parenthesis)

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Brazil, 1998Brazil, 1998

Laboratory evidence of HIV infection and CD4 cell count categories less than 350 cells/ mm³

or Oral cadidiasis and/or negative delayed

hypersensitivity test (DHT) or At least 3 of the following for > 1 month: generalized

lymphadenopathy; diarrhoea; fever; asthenia; night sweats;weight loss of more than 10% of body weight; invasive cervical cancer

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Limitations with current AIDS surveillance in low and middle income

counties

Limitations with current AIDS surveillance in low and middle income

counties Several different definitions of AIDS

Not all are biologically consistent (e.g. pTB, bacteria)

Haphazard self reporting systems with (very) incomplete data collection

Assumes a western natural history of disease - most morbidity is with an ADD

- all transit through AIDS to death

Provide an incomplete picture of burden of disease

None are congruent with WHO clinical staging

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Do we need AIDS surveillance?Do we need AIDS surveillance?

Clearly YES to have any handle on the epidemic of disease to capture changes in the burden of disease if we want to be able to show impact of ART

BUT it needs to be a better tool, more relevantto HIV disease process in resource-poor settings

It MUST BE consistent so trends can be compared

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Disease StagingDisease Staging

Hierarchical description of disease progression

Has prognostic significance for the patient

In clinical guidelines, help specify when to use antiretroviral therapy

Allows comparability in clinical trials– entry criteria– outcome– especially where immunological markers not

available

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WHO Clinical Staging SystemClinical Stage 1:AsymptomaticPersistent generalised lymphadenopathy (PGL)Performance scale 1: asymptomatic, normal activityClinical Stage 2:Weight loss, <10% of body weightMinor mucocutaneous manifestationsHerpes Zoster, within the last 5 yearsRecurrent upper respiratory tract infections (e.g. bacterial sinusitis)And/or performance scale 2: symptomatic, normal activity.Clinical stage 3:Weight loss, >10% of body weightUnexplained chronic diarrhoea, >1 monthUnexplained prolonged fever (intermittent or constant), > 1 monthOral candidiasis (thrush)Oral hairy leukoplakiaPulmonary tuberculosis, within the past year.Severe bacterial infections (e.g. pneumonia, pyomyositis)And/or Performance scale 3: bed-ridden, >50% of the day during the last monthClinical stage 4:HIV wasting syndrome, as defined by CDC1

Pneumocystis carinii pneumoniaToxoplasmosis of the brainCryptosporidiosis with diarrhoea, >1 monthCryptococcosis, extra pulmonaryCytomegalovirus (CMV) disease of an organ other than liver, spleen or lymph nodesHerpes Simplex Virus (HSV) infection, mucocutaneous >1 month, or visceral any durationProgressive multifocal leukoencephalopathy (PML)Any disseminated endemic mycosis (e.g. histoplasmosis, coccidioidomycosis)Candidiasis of the oesophagus, trachea, bronchi or lungsAtypical mycobacteriosis, disseminatedNon-typhoid Salmonella septicaemiaExtra Pulmonary tuberculosisLymphomaKaposi's sarcoma (KS)HIV encephalopathy, as defined by CDC2

And/or Performance scale 4: bed-ridden, >50% of the day during the last month

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Kaplan-Meier survival estimates, by stage

analysis time0 1 2 3 4

0.00

0.25

0.50

0.75

1.00stage 1

stage 2

stage 3

stage 4

Survival by clinical staging at enrolment in a cohort of 1371 HIV-infected Survival by clinical staging at enrolment in a cohort of 1371 HIV-infected adults from TASO, Entebbe in a trial of pneumococcal vaccineadults from TASO, Entebbe in a trial of pneumococcal vaccine

Time in years

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Limitations with current clinical staging

Limitations with current clinical staging

Staging needs revising - interim proposal from 1990(several inconsistencies and inaccuracies)

Stage 4 does not correspond with “AIDS”(no correspondence between staging & surveillance)

No clinical criteria proposed for how to establish presumptive or definitive staging diagnosis

Different trial centres using different approaches so results may not be easily comparable

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ConclusionsConclusions

HIV/AIDS disease and death has been largely ignored by epidemiologists

AIDS surveillance inconsistent and incomplete AIDS relates badly to clinical staging (confusing) Impact of HIV/AIDS on death rarely measured Approaches used have been non-standardised Projections and data cannot easily be compared

All this untenable as we enter the 3x5 ART era

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Strategic Information NeedsStrategic Information Needs

Revised and standardised AIDS case definitions Updated clinical staging with definitions

- must ensure staging and AIDS more compatible- do this for both adults and children

Agree practical approach to count HIV-related deaths in sentinel sites

Move fast to establish baselines and standards as interventions rapidly scaled up

24th June 2003 1 World Health Organization Clinical Staging, AIDS surveillance and Mortality in...

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