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- A Stuijt
- Retired South African medical journalist, ex-Sunday Times of Johannesburg.
XDR-TB epidemic spreads by shared hospital wards and workplaces…
00:29 | 
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A Stuijt |
Deadly, extensively drug-resistant tuberculosis is still emerging in SA “because of delays in diagnosis, sub-optimal treatment and poor infection control”-- not because patients fail to adhere to their drugs-regimen, a newly published study of XDR TB cases in a North West gold mine notes.
Keith Alcoln of AIDSMAP in the UK quotes from the latest study examining 128 gold-miners with drug-resistant TB at a single gold mine in North West province between January 2003 and November 2005… i.e. before the outbreak of XDR-TB in Tugela Ferry, KZN.
In South Africa, many tens of thousands of people a year now reportedly die of the co-infection of multiple-drug-resistant Tuberculosis together with AIDS – often within 32 days of diagnosis.
Previous reports have always claimed that patients developed drug-resistance because they did not adhere to the drugs-regimen.
However this new study shows that developing drug-resistance is not primarily the patient’s fault – they show that despite the high 85% cure-rate of ‘common’ TB at the West Vaal hospital (and also at Tugela Ferry), the poor infection controls by the SA health authorities themselves are causing the rapid spread of the deadly epidemic. It now has become the main cause of death in the country since it was first diagnosed in 2005.
South Africa shows the fastest rate of XDR-TB infection – however it is found in many other countries and is spreading even to countries with excellent TB-control: it has lately been identified among Eastern European migrants in the Netherlands, with 12 incurable cases in 2009; in France HIV-infected African migrants are the primary group being hit hard by TB co-infection – and the resulting multiple-drug-resistance is nearly incurable with existing drugs, these health authorities warn. The best way to control this airborne very infectious bacterial disease is to try and prevent it in the first place.
‘A cure rate above 85% – yet new cases of drug-resistant TB were still growing:’
The study by the US Centers for Disease Control ‘s online journal Emerging Infectious Diseases, noted that although the gold mine had achieved a cure rate above 85% in the treatment of new smear-positive ‘normal’ TB cases by 2001 using DOT treatment -- new cases still continued to rise and importantly, the cases of drug-resistant TB were also still growing.
Investigators from Stellenbosch University, Harvard University School of Public Health and West Vaal Hospital identified 128 drug-resistant TB cases among the 3,003 new TB cases notified at the gold mine’s hospital (West Vaal). Eighty-four also were co-infected with HIV, seven were HIV-negative and the remainder had an unknown HIV status (in South Africa patients are allowed to refuse HIV-testing under the privacy-law).
- Sixty-two per cent of those with MDR TB had a CD4 count below 200, indicating advanced HIV infection, but only 8% were already receiving antiretroviral therapy at the time of MDR TB diagnosis.
35% of these patients died, only 31% of those who were diagnosed with MDR TB were cured with the remainder still receiving treatment at the time of the analysis at the end of November 2005. However the cure-rates for MDR-TB are less than 2% in South Africa and in the KZN outbreak it was found that 95% of the patients who had advanced to incurable XDR-TB died within 32 days. Very likely all these gold-mine workers in the test-programme have died by now.
- The investigators calculated that 71% of these patients had acquired drug-resistant TB from another patient.
In the largest cluster of 42 patients, three-quarters of patients had been hospitalised for non-MDR TB in a general TB ward at the same time as another patient in the cluster was admitted to the hospital with Multiple-drug-resistant-TB care.
- Since all patients with TB received care on the same ward until diagnosed with MDR TB, it is not hard to see how such a large cluster could have emerged within a single facility, the researchers noted.
In addition 92% of MDR TB patients in the cluster had worked in the same mine shaft as another person in the same MDR TB cluster, and 85% lived in the same dormitory as another MDR TB case prior to diagnosis. Fifty-nine per cent of MDR TB patients in any cluster had a previous history of TB treatment.
The authors make a number of recommendations for curtailing the spread of MDR TB within South African hospitals and workplaces:
- Better infection control measures on general wards, outpatient waiting areas and TB wards.
- Ensure that everyone who is eligible for antiretroviral therapy is getting it, in order to reduce the number of individuals susceptible to developing active TB.
- Greater efforts to identify infectious cases through intensified case finding, active screening and improved education about TB symptoms.
- More frequent sputum smear examinations to identify infectious cases, and more frequent culture-based diagnosis to identify cases before they become infectious.
- Development and implementation of rapid drug susceptibility testing in order to identify MDR cases, plan appropriate treatment and separate from susceptible patients.
HALF OF ADULT HOUSEHOLD CONTACTS OF DRUG-RESISTANT TB in KZN SPREAD BY FAMILY MEMBERS
Approximately half of adult household contacts of drug resistant TB cases had resistance profiles that differed from the index case of TB, according to a presentation given by Dr. Tony Moll at the 40th Union World Conference on Lung Health in Cancún, Mexico.
“This discrepancy between drug resistance in index cases and their household contacts suggests community spread of MDR- and XDR-TB,” Dr. Tony Moll of the Church of Scotland Hospital in Tugela Ferry, South Africa, told the conference. http://www.aidsmap.com/en/news/A944FD07-8DDC-4AD3-B5B0-9E55FC3D2D5A.asp
The household contact tracing study was conducted in Msinga, a rural sub-district of KwaZulu Natal, where the annual TB case rate is 1,000 per 100,000 population and about 75% of TB patients are also infected with HIV.
- Since 2005, 852 drug resistant TB cases have been identified. Of these, 43% of these have been multidrug resistant TB (MDR-TB), and 57% extensively resistant (or XDR-TB).
Methods
In a four-year period from 2005-2008, the homes of each index case of multi- and extensively resistant TB cases were visited an average of 2-3 times, and every adult contact within the household was screened for TB (the study excluded children under the age of 13 due to the difficulty in diagnosing pulmonary TB in young children). A TB symptom history was conducted; sputa were collected on all sputum producers, and a chest X-ray was obtained for each adult contacts with productive cough or other signs and symptoms of tuberculosis. A physician evaluated each TB suspect.
Results
There were 711 index cases. Of these, 306 persons were identified as having MDR-TB: household contact tracing was possible in 255 (83%) of these cases but only 221 (72%) were included in the final analysis (some were excluded because there were no adults available for evaluation or missing data).
The remaining 405 index cases had XDR-TB: 333 (82%) of their households were traced, with 287 (71%) were included in the analysis. In all, 508 households were included in the study.
81% of the cases died within 32 days…
Nearly two-thirds (64%) of index cases were sputum smear-positive but only 50% had a previous history of TB, indicating transmission of already resistant strains in the 50% presenting with their first episode of TB. Eighty-one percent of index cases died with a median survival of only 32 days. http://www.aidsmap.com/en/news/A944FD07-8DDC-4AD3-B5B0-9E55FC3D2D5A.asp
There were 1059 adult household contacts among the MDR-TB cases: 793 (75%) were screened for respiratory symptoms and 773 (97%) provided sputum sample for culture and drug sensitivity testing.
- Among the 1372 household contacts of XDR-TB cases, 973 (71%) were available for screening and 940 (97%) provided sputum sample for culture and drug sensitivity testing (DST). In all, complete data was available for 1713 adult household contacts identified.
- A median of 79 days passed from sputum collection of the index case to identification of household contacts, although the time for the actual household contact tracing was usually within a week of the diagnosis of drug resistant TB in the index case. The delay in susceptibility testing prolonged the period of time during which household contacts were exposed to the drug-resistant TB case.
Contact tracing identified cases of TB in 55 (11%) households. Of these, 47 households had only one TB case, 14 had two cases and 1 household had 3 cases.
Although survival was better for household contacts compared to index cases, there was still significant mortality (14% of MDR-TB and 52% of XDR TB household cases, respectively) within the median 506 day follow-up period.
Notably about half of the household contact TB cases had DST results that were discordant from the household’s index case, suggesting possible transmission in other community settings. The spread of resistant TB within the community needs further investigation.
Limitations of the study included unknown HIV status on most household contacts, so there was no control for HIV infection in the comparison of outcomes in the survivors and index patients. The study considered only household contacts and not other casual or close contacts. The investigation provides a minimum estimate of the household contacts, as they were not able to find each household contact.
Discussion
Further studies are needed to examine prevention control at the household level. “This study underlies the need for earlier diagnosis, particularly in this setting where the mortality is so high in the index cases,” stated Dr. Tony Moll, the study investigator.
Today, the TB cure rate is 83% in Msinga and the default rate 0%. There are dedicated tracing teams to investigate households of resistant cases. The study team hopes to extend the household tracing to children and report on those results in a future meeting.http://www.aidsmap.com/en/news/A944FD07-8DDC-4AD3-B5B0-9E55FC3D2D5A.asp
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Reference Moll A et al. Results of contact investigation and follow-up of contacts of MDR-TB and XDR-TB patients in Kwazulu-Natal. 40th Union World Conference on Lung Health, Cancún, Mexico, 2009. Reference Calver AD et al. Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa. Emerging Infectious Diseases 16 (2): 264-271, 2010. http://www.aidsmap.com/en/news/D41DCB96-4856-4F88-B8E8-71512F289403.asp AND http://www.aidsmap.com/en/news/A944FD07-8DDC-4AD3-B5B0-9E55FC3D2D5A.asp
High TB-rates in France amongst HIV+ migrants from sub-Saharan countries: The incidence of tuberculosis (TB) amongst HIV-positive patients in France doubled between 1997 and 2008, investigators report in the January 28th edition of AIDS. During this period there was a particularly large increase in TB incidence among HIV-positive migrants, especially those from sub-Saharan Africa. A low CD4 cell count and a high viral load were risk factors for TB, and a large number of patients were diagnosed with HIV and TB at the same time. Treatment with anti-HIV drugs was associated with a lower risk of TB. The researchers believe that such findings warrant “the co-prescription of TB-preventative therapy and combination antiretroviral therapy for severely immunodepressed high-risk patients such as migrants and socially excluded patients”. Many of the cases of TB diagnosed amongst patients with HIV in France and similar countries are among migrants from countries with a high TB prevalence. French investigators designed a prospective study involving 72,580 HIV-positive adults who received care between January 1997 and December 2008. The proportion of patients who were migrants increased from 9% in 1997 to 29% in 2008. By this time 21% of all patients were from sub-Saharan Africa. A total of 2625 patients were diagnosed with TB. A little over a third (36%) of these had their TB and HIV diagnosed at the same time. During the period of analysis, overall TB incidence increased from 0.69 per 100 person years in 1997 to 1.39 per 100 person years in 2008. Incidence of TB amongst migrants was approximately twice that seen in non-migrants. In both groups of patients TB incidence increased – by 85% amongst non-migrants and by 151% in migrants. The only group of non-migrant patients in whom TB incidence did not increase significantly (p < 0. 0001) was gay men. When the investigators looked at the risk factors for TB, they found migrants from sub-Saharan Africa had twice the risk of TB compared to HIV-positive individuals born in France (adjusted risk ratio, 2.16; 95% CI, 1.88-2.48). Furthermore, the risk of TB was 83% higher amongst migrants from other regions compared to French-born patients with HIV. Late diagnosis of HIV was associated with an increased risk of TB for both migrants and non-migrants. The risk of TB was highest during the first six months of HIV care, and among patients with lower CD4 cell counts and higher viral loads (p < 0.0001 for all risk factors).
Patients who had been taking combination HIV treatment for at least six months had a 50% lower risk of TB compared to those not taking antiretroviral therapy (p < 0.0001).
Area of residence was also associated with TB risk, and was highest for those living in Paris or the French West Indies. Both these regions have large migrant populations.
“The incidence rates of TB among HIV-infected patients in this study was 40 times higher than those reported among the general population in France and 20 times higher than those reported in the Paris area…confirming that HIV itself is a risk factor for TB”, comment the investigators. In a third of patients, HIV was diagnosed at the same time as TB. “TB continues to reveal HIV in industrialised countries”, write the investigators. Late diagnosis of HIV is a matter of concern in many western European countries, and it is recommended that all patients diagnosed with TB should be offered an HIV test. All groups other than gay men had an increasing incidence of TB. Although the risk of TB fell the longer a patient received HIV treatment, the investigators note that, overall, TB incidence increased. They therefore conclude, “selected patients, such as migrants from highly endemic regions and patients with delayed access to care…might, therefore, benefit from co-prescription of TB-preventative therapy and combination antiretroviral therapy”.
ReferenceAbgrall S et al. HIV-associated tuberculosis and immigration in a high-income country: incidence trends and risk factors in recent years. AIDS 24 (online edition), 2010. http://www.aidsmap.com/en/news/8BA43F9B-0FA6-4CA0-A219-77784D20FA50.asp
- HIV-positive African migrants in France hit hard by TB
- Household contact tracing reveals extensive community spread of MDR and XDR TB in South Africa
- http://censorbugbear-reports.blogspot.com/2010/01/drug-resistant-tb-patients-died-within.html
- http://censorbugbear-reports.blogspot.com/2010/02/dutch-fans-to-wc2010-warned-of-tb.html
- http://censorbugbear-reports.blogspot.com/2008/09/killer-tb-epidemic-leading-cause-of.html
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