Cytomorphological changes Cytomorphological changes on conventional smears from on conventional smears from

HIV positive womenHIV positive womenDr Genevieve Warner Dr Genevieve Warner LearmonthLearmonth

University of Cape Town South AfricaUniversity of Cape Town South Africa

Royal Free Hospital LondonRoyal Free Hospital London

Aetiology of AIDSAetiology of AIDS

Up to 1984 all efforts to identify a causal Up to 1984 all efforts to identify a causal organism failed.organism failed.

A virus ( retrovirus ) was suspected - named A virus ( retrovirus ) was suspected - named

( Human T cell Leukaemia Virus HTLV III)( Human T cell Leukaemia Virus HTLV III) Research groups were unable to identify Research groups were unable to identify

HTLV III particles in excised lymph nodesHTLV III particles in excised lymph nodes Viruses were not well understood.Viruses were not well understood.

Burkitts lymphomaBurkitts lymphoma

Burkitt ( from Co: Fermanagh, Ireland) Burkitt ( from Co: Fermanagh, Ireland) noticed a strange disease, occurring in noticed a strange disease, occurring in children, across a definite geographical belt in children, across a definite geographical belt in Africa.Africa.

He proposed that it was either insect borne or He proposed that it was either insect borne or that it was an independently infective disease.that it was an independently infective disease.

It was eventually called Burkitt’s Lymphoma, It was eventually called Burkitt’s Lymphoma, caused by a caused by a virus ( EBV)virus ( EBV)

Along came Acquired Along came Acquired Immunodeficiency Disease Immunodeficiency Disease

Syndrome ( AIDS)Syndrome ( AIDS) This was characterised by a prodromal phase This was characterised by a prodromal phase

of unexplained lymphadenopathy and of unexplained lymphadenopathy and deteriorating immune function resulting in deteriorating immune function resulting in severe rampant infections :severe rampant infections :

STD’s, TB, Fungal infections, unusual STD’s, TB, Fungal infections, unusual parasitic diseases, Kaposi’s sarcoma , parasitic diseases, Kaposi’s sarcoma , lymphoma.lymphoma.

Retrovirus ?Retrovirus ?

In1984 Tom Warner, In1984 Tom Warner, pathologist from pathologist from Galway, Ireland was the Galway, Ireland was the first researcher to first researcher to describe and photograph describe and photograph a D-type a D-type retrovirus, retrovirus, in in association with association with dendriticdendritic reticulum cells reticulum cells within lymph nodes from within lymph nodes from patients with prodromal patients with prodromal AIDS.AIDS. Lymphoid tissueLymphoid tissue

If you look carefully Dendritic Cells are If you look carefully Dendritic Cells are easy to observe on cervical smears!easy to observe on cervical smears!

Cervical Smear, AIDS patient

Dysfunctional Metabolism in Dysfunctional Metabolism in HIV/AIDSHIV/AIDS

Malabsorbtion of VitaminsMalabsorbtion of Vitamins Vitamin A deficiency: disorders of Vitamin A deficiency: disorders of

keratinisationkeratinisation Vitamin B deficiency: disorders of bone Vitamin B deficiency: disorders of bone

marrow function – macrocytic cellsmarrow function – macrocytic cells Vitamin B6 Folic acid deficiency: cytomegalyVitamin B6 Folic acid deficiency: cytomegaly Vitamin C deficiency: scurvy, Vitamin C deficiency: scurvy,

The effects of dysfunctional metabolism The effects of dysfunctional metabolism are reflected in cytomorphological are reflected in cytomorphological changes in surface epithelial cellschanges in surface epithelial cells

Dendritic cells --- increased numberDendritic cells --- increased number Abnormal keratinisation --- intense Abnormal keratinisation --- intense

orangeophiliaorangeophilia Cytomegaly --- macrocytes ( Jumbo cells),Cytomegaly --- macrocytes ( Jumbo cells),

causing confusion with HSILcausing confusion with HSIL Binucleate and multinucleated cellsBinucleate and multinucleated cells

If you know what you are searching If you know what you are searching for, keep looking !for, keep looking !

Infection and Dendritic CellsInfection and Dendritic Cells

Dendritic cellsDendritic cellson cervical smearson cervical smears

Dendritic cytoplasmic Dendritic cytoplasmic processesprocesses

Basophilic cytoplasm,Basophilic cytoplasm, Regular nuclear Regular nuclear

membranesmembranes Multiple small nucleoliMultiple small nucleoli

Hyperkeratosis in HIV “Warty atypia”Hyperkeratosis in HIV “Warty atypia”abnormal keratin productionabnormal keratin production

dyskeratosisdyskeratosis

Abnormal Keratinization in most Abnormal Keratinization in most cells great and small cells great and small

Intense orangeophilia:Intense orangeophilia:excessive keratinizationexcessive keratinization

Squamous pearls, and dysplastic Squamous pearls, and dysplastic cells containing glycogencells containing glycogen

HIV and CytomegalyHIV and Cytomegaly

Generalised marked Generalised marked enlargement of cells --- enlargement of cells --- compare with size of compare with size of erythrocyte or erythrocyte or polymorph.polymorph.

Enlarged cells with normal N/C ratioEnlarged cells with normal N/C ratio

Binucleate cells small and largeBinucleate cells small and large

Enlarged cells have also Enlarged cells have also been reported in bone been reported in bone marrow aspirates in marrow aspirates in HIV infected persons.HIV infected persons.

Often called Often called MACROCYTES.MACROCYTES.

Huge binucleate macrocytic Huge binucleate macrocytic squamous cells, nuclear cytoplasmic squamous cells, nuclear cytoplasmic

ratio suggests LSILratio suggests LSIL

Metaplastic and dysplastic Metaplastic and dysplastic (LSIL)(LSIL) macrocytic squamous cellsmacrocytic squamous cells

Huge Bizarre CellsHuge Bizarre Cells

HIV and HPVHIV and HPV

Is this HPV koilocytic Is this HPV koilocytic change,change,

or is it Folic Acid or is it Folic Acid Deficiency ( FAD ) Deficiency ( FAD ) change?change?

Or this a reflection of Or this a reflection of multiple infections and multiple infections and deficienciesdeficiencies

Bizarre nuclei in large cells, plentiful Bizarre nuclei in large cells, plentiful cytoplasmcytoplasm

The effects of the dysfunction caused by The effects of the dysfunction caused by malnutrition, vitamin deficiency and malnutrition, vitamin deficiency and

infection are reflected in epithelial cellsinfection are reflected in epithelial cells

These changes are most easily seen on These changes are most easily seen on Cytology specimens: cervical smears, blood Cytology specimens: cervical smears, blood smears, marrow smears, brain smears.smears, marrow smears, brain smears.

This cellular material can be archived for This cellular material can be archived for bacterial, viral, and genome, studies. bacterial, viral, and genome, studies.

TB screening ( sputum smears)TB screening ( sputum smears)

Solutions to the AIDS /HIV epidemicSolutions to the AIDS /HIV epidemic

?Vaccines --- rapid ?Vaccines --- rapid mutation of the virusmutation of the virus

?Anti Retroviral?Anti Retroviral Drugs Drugs --- “miraculous --- “miraculous recovery of well being”recovery of well being”

Education --- self care, Education --- self care, diet, cultural, sexual diet, cultural, sexual behaviour, behaviour,

CONDOMSCONDOMS – – “weapons of mass“weapons of mass protection”protection”

Remote rural populations, with no Remote rural populations, with no infrastructureinfrastructure

Anti Retroviral Drug Therapy Anti Retroviral Drug Therapy (ARVD)(ARVD)

In 2003 ---- protest to Government for failure In 2003 ---- protest to Government for failure to distribute free ARVD’s . Global pressureto distribute free ARVD’s . Global pressure

ARVD’s were available in some areas of SA ARVD’s were available in some areas of SA “at a price”“at a price”

Medical personnel joined in the protestMedical personnel joined in the protest Marched on the opening of parliament in Cape Marched on the opening of parliament in Cape

Town in February 2004Town in February 2004

Availability of ARVD’sAvailability of ARVD’s

Following negotiations ARVD’s were quickly made Following negotiations ARVD’s were quickly made available.available.

Availability was excellent Availability was excellent Small financial cost to offset a huge human cost Small financial cost to offset a huge human cost HOWEVERHOWEVER No time for education !!!No time for education !!! No time for proper infrastructure .No time for proper infrastructure . No ethical consideration.No ethical consideration.

Women with HIV in AfricaWomen with HIV in Africa Three weeks of ARVD therapy ---- good complianceThree weeks of ARVD therapy ---- good compliance ARVD’s DO NOT KILL THE HIV virus.ARVD’s DO NOT KILL THE HIV virus.

Women feel well , return to “normal living”Women feel well , return to “normal living” Caring for their children and ill relatives, Caring for their children and ill relatives, Engage in sex, spread AIDS new partners.Engage in sex, spread AIDS new partners. Become pregnant --- infants infectedBecome pregnant --- infants infected

CONDOMS "CONDOMS "weapons of mass protectionweapons of mass protection“ are not “ are not yet universally accepted.yet universally accepted.

Fate of women on ARVD’sFate of women on ARVD’s

Unprotected Sexual intercourseUnprotected Sexual intercourse Pregnant , Poverty, PowerlessPregnant , Poverty, Powerless Fertility RateFertility Rate is very high despite metabolic is very high despite metabolic

dysfunction and multiple infections.dysfunction and multiple infections. This phenomenon has been noticed during This phenomenon has been noticed during

other epidemics and famines --- Irish famine other epidemics and famines --- Irish famine (1840), famines in Africa 20(1840), famines in Africa 20 thth century century

Result of Freely available ARVD’s Result of Freely available ARVD’s

Migration of HIV/AIDS refugees to HIV/AIDS Migration of HIV/AIDS refugees to HIV/AIDS “settlements”“settlements”

Medical Resources stretched.Medical Resources stretched. Huge increase in the number of survivors needing Huge increase in the number of survivors needing

long term care.long term care. Massive increase in Cervical Smears from women Massive increase in Cervical Smears from women

with HIV/AIDS --- this provideswith HIV/AIDS --- this provides (1) further insight into the nature of the disease and (1) further insight into the nature of the disease and

the resultant social dysfunction.the resultant social dysfunction. (2) archive material for further research(2) archive material for further research

Tuberculosis “ a terrible twin”, which occurs Tuberculosis “ a terrible twin”, which occurs in a large percentage of Patients with in a large percentage of Patients with

HIV/AIDSHIV/AIDS Tuberculosis is a highly Tuberculosis is a highly

contagious airborne disease, contagious airborne disease, associated with poverty, associated with poverty, pregnancy, reduced pregnancy, reduced immunity and malnutritionimmunity and malnutrition

Tuberculosis and povertyTuberculosis and poverty

TB bacilli on sputum smear

OutcomeOutcome

Epidemics of HIV and TB gather momentumEpidemics of HIV and TB gather momentum Tuberculosis becomes resistant: MDR TBTuberculosis becomes resistant: MDR TB In Zululand: XDR TBIn Zululand: XDR TB Resurgence of LeprosyResurgence of Leprosy

Will the HIV epidemic behave like other Will the HIV epidemic behave like other epidemics and “Burn itself out ?”epidemics and “Burn itself out ?”

The only solution The only solution

Education Education EmpowermentEmpowerment Emancipation – Emancipation –

“weapons of mass “weapons of mass protection”protection”

Eyes “Look at the world Eyes “Look at the world with new eyes”with new eyes”