Post on 27-Mar-2015
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
World Health Organization
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
24th June 2003 3
World Health Organization
24th June 2003 4
World Health Organization
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
24th June 2003 5
World Health Organization
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
24th June 2003 6
World Health Organization
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
...
24th June 2003 7
World Health Organization
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
24th June 2003 8
World Health Organization
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
24th June 2003 9
World Health Organization
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
24th June 2003 10
World Health Organization
European case definition, 1993European case definition, 1993
Same as CDC 1993 minus CD4 cell count
24th June 2003 11
World Health Organization
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
24th June 2003 12
World Health Organization
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
24th June 2003 13
World Health Organization
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)
24th June 2003 14
World Health Organization
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
24th June 2003 15
World Health Organization
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
24th June 2003 16
World Health Organization
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
24th June 2003 17
World Health Organization
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
24th June 2003 18
World Health Organization
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
24th June 2003 19
World Health Organization
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
24th June 2003 20
World Health Organization
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
24th June 2003 21
World Health Organization
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
24th June 2003 22
World Health Organization
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