charlie gilks stagingsurveillance

8/12/2019 Charlie Gilks Stagingsurveillance

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World Health Organization

Clinical Staging, AIDS surveillance and

Mortality in resource-poor settingsa clinicians view of strategic information needs

Charlie Gilks

Surveillance, Research Monitoring and Evaluation

Department of HIV/AIDS


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Some 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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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 HUGEadvocacy tool


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Annual number of reported HIV-relateddeaths, USA, 1991-2001

0

10,000

20,000

30,000

40,000

50,000

60,000

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Source: CDC Surveillance Reports, 1 991-2001

N

umberofHIV-relateddeaths


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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 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) is

nota single disease entity but a surveillance definition

The CDC case definition has changed 3 times


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CDC case definition, 1993

Laboratory evidence of HIV infection; and

CD4 cell count less than 200 cells/ mm orCD4 cells account forfewer 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 (greaterthan 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 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

Numberofrepor

tedAIDScases

0

5

10

15

20

25

30

35

40

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Source: CDC Surveillance Reports, 1991-2001

ReportedAID

Scasesper

100,000population


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European case definition, 1993

Same as CDC 1993 minus CD4 cell count


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WHO case definition for AIDSsurveillance (Bangui)

At least 2 major signsin 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

Orgeneralized KS or cryptococcal meningitis


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Expanded WHO case definition for AIDSsurveillance (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; Cryptoccocalmeningitis; pulmonary or extra-pulmonary TB; KS; Neurologicalimpairment sufficient to prevent independent daily activitiesnot 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

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 withcavitation or unspecified (5); Herpes zoster in person of 60 years orless (5); central nervous system dysfunction (5); diarrhoea > 1 month(2); fever at least 38 for at least a month (2); cachexia or weight lossof more than 10% (2); asthenia of at least a month (2); persistentdermatitis (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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Limitations with current AIDS surveillance inlow 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?

ClearlyYES 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 ARTBUT it needs to be a better tool, more relevant

to HIV disease process in resource-poor settings

It MUST BEconsistent so trends can be compared


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Disease 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

WHO Cli i l St i S t


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WHO Clinical Staging SystemClinical Stage 1:

Asymptomatic

Persistent generalised lymphadenopathy (PGL)

Performance scale 1: asymptomatic, normal activity

Clinical Stage 2:

Weight loss, 10% of body weight

Unexplained chronic diarrhoea, >1 month

Unexplained prolonged fever (intermittent or constant), > 1 month

Oral candidiasis (thrush)

Oral hairy leukoplakia

Pulmonary 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 pneumonia

Toxoplasmosis of the brain

Cryptosporidiosis with diarrhoea, >1 month

Cryptococcosis, extra pulmonary

Cytomegalovirus (CMV) disease of an organ other than liver, spleen or lymph nodes

Herpes Simplex Virus (HSV) infection, mucocutaneous >1 month, or visceral any duration

Progressive multifocal leukoencephalopathy (PML)

Any disseminated endemic mycosis (e.g. histoplasmosis, coccidioidomycosis)

Candidiasis of the oesophagus, trachea, bronchi or lungsAtypical mycobacteriosis, disseminated

Non-typhoid Salmonella septicaemia

Extra Pulmonary tuberculosis

Lymphoma

Kaposi's sarcoma (KS)

HIV encephalopathy, as defined by CDC2

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

Survival by clinical staging at enrolment in a cohort of 1371 HIV-infected


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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

adults from TASO, Entebbe in a trial of pneumococcal vaccine

Time in years


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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 approachesso results may not be easily comparable


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Conclusions

HIV/AIDS disease and deathhas been largelyignored 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 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 standardsas interventions rapidly scaled up

charlie gilks stagingsurveillance

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