Extensively drug-resistant Mycobacterium tuberculosis : Transmission and Mortality
Extensively drug-resistant Mycobacterium tuberculosis transmission is causing high mortality in co-infected patients with HIV- 1 and threatens success for treatment programs.
INTRODUCTION
Tuberculosis is on the most tenacious infectious
diseases and it continues to advance with increase
vigor. One in three people in the world are
infected with dormant TB. Globally, the disease
annually continues to claim the lives of over 2
million people. Tuberculosis is often
underestimated and underfunded with respect to
foreign aid.
Treatment of TB calls for special drugs:
•  3 to 4 anti-tuberculosis drugs have to be administered
simultaneously over a period of six months. Standard
treatment is ethambutol, pyrazinamide, isoniazid,
rifampicin.
• Its not uncommon for treatment to fail because of
lack of compliance on the part of the patient. WHO
has suggested and implemented programs like DOTS
“directly observed treatment short course” patients
must take their medications in the presence of medical
providers.
• Inadequate compliance has lead to a dramatic
increase in mono-resistant organisms (MDR)-TB .
The drug-cocktail allows for multi-resistance to
develop very quickly. Once this happens only second
line drugs will help. More recently researchers have
found emerging resistance to second line antibiotics,
termed extensively drug-resistant (XDR)-TB
tuberculosis.
Figure 1. The Distribution of culture results and drug-
resistance categories by group for all patients. (n=1539).
Among confirmed cases 39% MDR and 6% XDR.
The World Health Organization has announced XDR-
TB is like “ebola with wings” and is immanent threat
to society. This paper addresses the current prevalence
.
of MDR tuberculosis and XDR tuberculosis in this
rural area in South Africa. A population has shown to
have high rates of HIV co-infected patients that are
associated with high rates of mortality.
TEMPLATE DESIGN © 2008
www.PosterPresentations.com
Meridith Hallowell
METHODS PATIENT DEMOGRAPHICS CONCLUSIONS
The prevalence of XDR-TB is much high than expected.
53 patients with XDR: It was found 10% of TB- positive sputum. Tuberculosis is
Sputum samples were obtained for mycobacterial the most common opportunistic infection for individuals
•  49% were women
culture and drug susceptibility testing. Samples were with HIV. HIV positive individuals are at high risk for
• Median age 35
taken from Msinga sub-district of KwaZulu Natal, illness and mortality if exposed. Antiretroviral therapy
•  Majority of patients 55% had never received
South Africa at a government-sponsored tuberculosis can improve mortality in co-infected patients but
treatment for TB.
treatment program, using the WHO DOTS strategy treatment is less successful in patients with MDR. MDR
• 30% had documentation of cure or completion of treatment uses second line drugs and is not a readably
and patients receive free treatment for tuberculosis.
tuberculosis treatment course. available treatment. There are very few drugs that can
• All cases came from dispersed geographical locations,
There were three groups successfully treat XDR, and in this study has shown to be
no known other than the hospital. fatal in almost all cases. This study provides insight into
•  No patients has a family member who was or
•Group one: Individuals with persistently smear- future public health consequences especially in areas with
currently is sick with tuberculosis a high prevalence of HIV. More than half the patients
positive sputum specimens
•  100% of the 44 out 44 tested XDR-TB patients with XDR-TB had never previously been treated for TB.
tested positive of HIV.
•Group two: all inpatients present on the male and 100% of the patient sputum tested for HIV were positive,
indicating a significant correlation between XDR-TB
female tuberculosis wards on a single day and those
transmission and HIV.
with recurrent tuberculosis. MORTALITY
A third of the patients had either been cured or completed
•Group three: consecutive inpatients who presented
treatment for TB. This is higher than expected, indicating
with signs and symptoms of tuberculosis higher transmission rates verses unsuccessful treatment.
Additionally, only 15% of patients had failure to complete
Genotyping by IS6110 fingerprinting 20 and Died treatment. Most patients were unlikely to have developed
spoligotyping 21 was done on isolates found to have the XDR- Strain because of unsuccessful treatment. 85%
resistance to first-line and second-line drugs. Based on Survived of XDR isolates were from the KZN family. KZN strains
the resistance researchers determined prevalence rates were either susceptible or resistant to first line drugs.
of MDR and XDR tuberculosis among confirmed Indicating a recent transmission of XR-TB to patients. All
tuberculosis cases. patients it is likely that the transmission occurred
Figure 3 Mortality after sputum collection in patients nosocomially. All the the patient were admitted at the
with XDR-TB (n=53). 52 of 53 pts with XDR-TB died, same hospital. This is similar to historical out breaks of
98% morality. MDR-TB worldwide, in which drug resistant strains are
RESULTS known for transmitting nosocomially.
PREVALANCE
There are three main improvements that need be
approached to reduced the effects of MDR and XDR
tuberculosis.
Proportion surviving
1.  Increase infection control in areas with XDR or
MDR
2.  Better treatment programs to reduce the
probability of more strains of MDR and XDR
3.  Accelerated development of drugs and treatment
for XDR and MDR
Patients with XDR have few available treatment options.
New treatments need to be developed as well as
accelerated diagnostic technology. The current testing
process requires microbial cultures a which are slow and
Days since sputum collected costly. Without rapid compressive tests it allows for
increased disease transmission opportunity.
Outbreaks, will continue to get worse as the fatal disease
Figure 4 Survival after sputum collection in patients is transmitted, especially in areas with high prevalence of
with XDR-TB with confirmed dates of death (n=42). HIV. It is crucial that improvements are made soon to
Multi-drug
Median survival time after specimens were collected break the cycle of transmission of drug–resistant
resistant
was 16 days. Roughly, 70% of the patients died in 30 tuberculosis.
Extensively
days. REFERENCES
drug-resistant
No drug
resistantance Eker B, Ortmann J, Migliori GB, et al. Multidrug-
and extensively drug-resistant tuberculosis,
GENOTYPING
Germany. Emerg Infect Dis 2008; 14: 1700–1706.
Gandhi NR, Moll A, Sturm AW, et al. Extensively
Figure 2. The prevalence of drug-resistant
m.tuberculosis in positive sputum cultures. Out of Genotyping shows that 39 of the 46 isolates tested of drug- resistant tuberculosis as a cause of death in
patients co-infected with tuberculosis and HIV in a
the 2203 sputum specimens there were 1539 XDR-TB tested genetically similar. They belonged to
patients. 542 patients had at least one culture the same family of KZN strain. (Fingerprinting was rural area of South Africa. Lancet 2006; 368: 1575–
positive for m.tuberculosis. In total 221 cases of 1580.
done on 16 of the 23 patients of group 1 and group 2.
MDR were identified. Additionally, 53 patients had Kaufmann, S. H. E., and Susan Schädlich. The New
All 30 patients of group 3 were tested).
XDR tuberculosis. Plagues: Pandemics and Poverty in a Globalized
World. London: Haus, 2009.