Uncovering XDRTB associated with HIV infection in KZN' Experience in KwaZuluNatal South Africa

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Uncovering XDRTB associated with HIV infection in
KZN. Experience in KwaZulu-Natal South Africa

• 4th Regional Advisory Panel (RAP)
• Regional Clinical Coordination sub-committee
  (RCCC)
• Meeting
• January 19, 2007
• Accra, Ghana
• Presented by Dr Tony Moll

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Community Setting

• KwaZuluNatal Msinga district
• 2,000 sq km rural district
• Rural community 300,000
• High prevalence TB
• TB case rate 800-1,000/100,000
• High prevalence of HIV
• 25 in antenatal attendees

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Background

• HIV and Tuberculosis (TB) epidemics in South
  Africa closely intertwined
• Up to 80 of new TB cases in KwaZulu Natal
  coinfected with HIV
• Annual mortality rate among coinfected patients
  up to 40 before antiretroviral (ARV) medications
• A large proportion of these deaths have been
  attributed to end-stage AIDS

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Background

• In a TB/ARV integration study mortality reduced
  to 12
• After 16 years of palliative care , ARV ushered
  fresh hope.
• 2 patients had excellent virologic response to
  ARV with undetectable HIV viral loads.
• However having marked clinical deterioration of
  TB signs and symptoms

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Inpatient Snapshot

• We suspected MDR-TB
• We did a snap shot across our TB wards
• 45 sputum samples submitted ( 7 Feb 05)
• Including 2 HIV/TB study patients
• We were expecting MDRTB
• 10 of the 45 patients had resistance to 6 drugs
  (INH,RIF,STREP,KANA,CIPR,ETH.)
• This uncovered the presence of moderately
  extended drug resistant TB in our hospital

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Snapshot results

• 10 of the 45 patients had resistance to 6 drugs
  (INH,RIF,STREP,KANA,CIPR,ETH.)
• This uncovered the presence of extended drug
  resistant TB in our hospital

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Objectives

• To assess the extent of MDR TB and XDR TB among
  patients presenting to a rural district hospital
  in KwaZulu Natal, South Africa
• To describe patient and treatment characteristics
  of patients with XDR TB

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Methods

• Isolates collected for mycobacterial culture
  (MGIT) of all TB suspects
• Period from January 2005 to March 2006 at a rural
  district hospital

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Methods

• Drug susceptibility testing performed on all
  cultures positive for M. tuberculosis
• Isoniazid, rifampicin, ethambutol, streptomycin,
  ciprofloxacin, kanamycin
• Chart review performed for patients with strains
  resistant to all tested drugs (XDR TB cases)
• Demographics, prior TB treatment, prior hospital
  admissions, HIV status, survival
• Molecular fingerprinting by spoligotyping on all
  XDR TB isolates

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1539 Patients with isolates sent
(June 05-Mar06)
RESULTS
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1539 Patients with isolates sent
544 (35) Culture-Positive for M.tb
995 (65) Culture-Negative
RESULTS
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1539 Patients with isolates sent
544 (35) Culture-Positive for M.tb
995 (65) Culture-Negative
221(41) Resistant to Isoniazid Rifampicin
(MDR TB)
323(59) Not resistant to both Isoniazid and
Rifampicin
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1539 Patients with isolates sent
544 (35) Culture-Positive for M.tb
995 (65) Culture-Negative
221(41) Resistant to Isoniazid Rifampicin
(MDR TB)
323(59) Not resistant to both Isoniazid and
Rifampicin
53 (24 of MDRTB, 10of culture positive)
Resistant to all tested drugs (XDR TB)
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Demographics of XDR TB Patients
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Prior TB Treatment
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New Infection with XDR TB

• Majority either never previously treated or had
  previous cure or treatment completion
• Suggests newly infected with drug-resistant TB
  strains
• Not development of drug resistance on therapy

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Transmission of XDR TB

• 64 of patients hospitalized for any cause before
  onset of XDR TB
• 2 healthcare workers died with confirmed XDR TB
• 4 other workers died with suspected MDR TB
• Nosocomial transmission in hospitals probable
• Transmission in community also possible since 36
  XDR TB patients with no prior hospitalizations

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Molecular Fingerprinting

• 26 of 30 (87) XDR TB isolates found to be
  genetically similar (KZN Strain)
• (identified 1995 by Prof Sturm)
• Suggestive of recent infection with
  drug-resistant strain

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Molecular Fingerprinting

• 26 of 30 (87) XDR TB isolates found to be
  genetically similar (KZN Strain)
• (identified 1995 at UKZN)
• Suggestive of recent infection with
  drug-resistant strain

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HIV Characteristics
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Mortality

• 52 of 53 (98) XDR TB patients have died
• Median survival from sputum collection 16 days
  (range 2-210 days)
• (Note this is not from time of infection with
  XDRTB )
• No significant difference by demographics, data
  collection group, previous TB or
  hospitalizations,
• HIV status, or use of ARVs

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Survival from Sputum Collection
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Survival from Sputum Collection
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MDR TB COSH MSINGA STATS ( January 2005
to 15 Dec 06)

• Total MDR XDR TB 369
• MDR-TB Total MDR TB 166 (45)
• Total MDR TB Deaths 112 (68 mortality)
• Total MDR TB on Rx 54 (32 survival)
• XDR-TB Total XDR TB 203 (55)
• Total XDR TB Deaths 171 (84 mortality)
• Total XDR TB on Rx 32 (16 survival)
• Total no. of contacts traced 1694
• Total no. of contacts with MDR TB 12
• Total no. of contacts with XDR TB nil

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MDR-TB COSH MSINGA (STATS) ( January 2005
to 15 Dec 06)

• Total MDR XDR TB 369
• MDR-TB Total MDR TB 166 (45)
• Total MDR TB Deaths 112 (68 mortality)
• Total MDR TB on Rx 54 (32 survival)
• XDR-TB Total XDR TB 203 (55)
• Total XDR TB Deaths 171 (84 mortality)
• Total XDR TB on Rx 32 (16 survival)
• Total no. of contacts traced 1694
• Total no. of contacts with MDR TB 12
• Total no. of contacts with XDR TB nil

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MDR TB COSH MSINGA STATS ( January 2005
to 15 Dec 06)

• Total MDR XDR TB 369
• MDR-TB Total MDR TB 166 (45)
• Total MDR TB Deaths 112 (68 mortality)
• Total MDR TB on Rx 54 (32 survival)
• XDR-TB Total XDR TB 203 (55)
• Total XDR TB Deaths 171 (84 mortality)
• Total XDR TB on Rx 32 (16 survival)
• Total no. of contacts traced 1694
• Total no. of contacts with MDR TB 12
• Total no. of contacts with XDR TB nil

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MDR TB COSH MSINGA STATS ( January 2005
to 15 Dec 06)

• Total MDR XDR TB 369
• MDR-TB Total MDR TB 166 (45)
• Total MDR TB Deaths 112 (68 mortality)
• Total MDR TB on Rx 54 (32 survival)
• XDR-TB Total XDR TB 203 (55)
• Total XDR TB Deaths 171 (84 mortality)
• Total XDR TB on Rx 32 (16 survival)
• Total no. of contacts traced 1694
• Total no. of contacts with MDR TB 12
• Total no. of contacts with XDR TB nil

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• Is XDR-TB a super-bug?

• XDR-TB
• is not more contagious
• than TB or MDR-TB

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• Is XDR-TB a super-bug?

• XDR-TB
• is not more contagious
• than TB or MDR-TB

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Association of HIV and TB TB infection to TB
disease

• 10 HIV(-) people develop active TB disease in a
  lifetime
• 15 HIV() people develop TB disease in a year
• In patients presenting with TB disease 80 are
  HIV pos
• In the first year after HIV infection, chances of
  developing TB disease is doubled
• After TB disease there is 10X higher chance of
  catching TB again than HIV(-) patient

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HIV Positive patients

• TB disease progresses faster
• TB more easily spreads to other organs
• TB most common opportunistic infection
• TB is the most common cause of death

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Summary

• Multidrug-resistant TB substantially more common
  in a rural district of KwaZulu Natal compared
  with previously published rates
• An extensively drug-resistant strain of TB
  accounts for nearly one-quarter of all MDR TB
  cases found
• Recent transmission in both hospital and
  community
• All patients HIV tested were HIV-infected
• Rapidly fatal

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Implications

• MDR XDR TB have emerged as significant causes
  of death among TB/HIV coinfected patients
• Sputum culture and drug susceptibility testing is
  needed to identify MDR XDR TB
• Success of ARV and TB DOTS programs threatened by
  MDR XDR TB
• Transmission of MDR and XDR TB must be addressed
  to further improve survival for HIV coinfected
  patients

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Merci, Abrigado, Thank you

• 4th Regional Advisory Panel (RAP)
• Regional Clinical Coordination sub-committee
  (RCCC)
• Meeting
• January 19, 2007
• Accra, Ghana
• Presented by Dr Tony Moll (tonymoll_at_telkomsa.net)