Household contact tracing of XDR and MDR-TB index patients in KwaZulu-Natal, South Africa
by Lois Eldred.
Lois Eldred is Associate Professor of Medicine and Epidemiology at the Center For TB Research, Johns Hopkins University School of Medicine, Baltimore.
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,” stated Dr. Moll of the Church of Scotland Hospital in Tugela Ferry, South Africa. The household contact tracing study was conducted in Msinga, a rural sub-district of KwaZulu Natal, where the annual TB case rate is over 1,000/100,000 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.
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.
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 resistantTB 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% and 52% of MDR-TB XDR and 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.
|
Contacts of MDR-TB index cases with positive TB Culture (N =32) |
Contacts of XDR TB index cases with positive TB Culture (N=32) |
|
|
Sensitive or mono-resistant TB cases |
2 (6%) |
2 (6%) |
|
MDR-TB |
14 (44%) |
8 (25%) |
|
XDR-TB |
10 (31%) |
19 (59%) |
|
Susceptibility pattern unavailable |
6 (19%) |
3 (9%) |
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 strong commitment by the district managers of the TB program is a key part of its success,” said Dr. Moll. The study team hopes to extend the household tracing to children and report on those results in a future meeting.
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.
Improving contact screening and isoniazid use in the Indian TB control programme
By Lois Eldred
India is home to 21% of the world’s tuberculosis cases, with 1.8 million new cases diagnosed each year, yet the case notification for children is less than 2%, according to a presentation given by Dr. Soumya Swaminathan at the 40th Union World Conference on Lung Health in Cancun, Mexico.
“Contact tracing could greatly improve the number of children identified with tuberculosis,” said Dr Swaminathan, who has recently joined the World Health Organization, “and preventive therapy could decrease childhood TB, though both interventions are underutilised.”
Background
The Indian Revised National TB Control Program (RNTCP) recommends household contact tracing of smear-positive pulmonary TB cases to identify adults and children at high risk for TB; it also recommends that six months of isoniazid preventive therapy (IPT) be administered for asymptomatic children under six years of age.
Dr. Swaminathan and her former colleagues at the Tuberculosis Research Centre in Chennai conducted a study in two rural and two urban TB units in the state of Tamil Nadu to assess whether the RNTP’s child contact screening and IPT policy is being implemented.
The study
Using TB treatment registers and patient treatment cards, they identified smear positive TB patients who started treatment between April and June 2008. Among the 253 TB patients identified, there were 607 adult household contacts and 136 children, of whom 84 were less than six years old.
Twenty-four percent of patients were informed by health care workers that their close contacts needed screening; 14% of child contacts aged 0-14 were screened for TB. Only 19% of children under six years old were initiated on IPT.
In focus groups with health care workers, differences in knowledge and performance were noted between rural and urban health workers — with rural health care workers being more reluctant to screen for TB and less aware of the concept of initiating IPT for children under six.
An assessment of the procedures for screening and delivering IPT found some critical gaps— for example, there was no mechanism for the periodic follow-up of children on IPT, or for ensuring drug intake.
None of the patient treatment cards documented the details of contact screening, administration of IPT, drug monitoring or follow-up. Completion of IPT often ended after treatment of the index case was completed, whether or not the child had completed the recommended six months of IPT.
Implications
Dr Swaminathan believes that simple lessons can be drawn from the study and lead to practical recommendations that — if implemented — could improve the rate of household contact tracing and implementation of IPT in young children.
For instance, creating a separate treatment card for contacts and children receiving chemoprophylaxis should be developed.
Training on contact tracing and IPT should be given a high priority, particularly in rural districts.
Health workers need to be reassured that every child does not need to be seen by a physician before initiating IPT.
“This information is timely”, Dr Swaminathan concluded, “and can be particularly useful to the World Health Organization as it develops its revised contact tracing guidelines in the coming months.”
Tuberculosis and HIV within prisons skyrocketing, a public health threat
By Mara Kardas-Nelson
Overcrowding, low access to health care, lack of political will and the prominence of high-risk populations among prisoners all contribute to a “perfect storm” for HIV and TB infection among prison populations worldwide, researchers announced at the 40th Union World Conference on Lung Health in Cancun, Mexico.
Dr. Fabienne Hariga of the UN Office on Drugs and Crime and UNAIDS’ Dr. Alasdair Reid both highlighted dismal health statistics for those behind bars. According to Hariga, up to 65% of some prison populations are infected with HIV.
Adding to this, says Reid, TB rates in prisons are up to fifty times higher than in the general population. Increased rates are found in prisoners who have served longer sentences, tying TB acquisition with prison time. Prisoners are also more likely to die from TB and/or default from treatment than non-incarcerated populations.
Dr. Hariga insists that such poor indicators not only pose a threat to prisoners’ health, but the health of the general public as well. Given the high rate of return to society, prisoners’ HIV and TB are easily spread to communities.
Prison staff are also affected by the high incidence of HIV and TB. Dr. Salome Charalambous of South Africa, speaking about HIV and TB prison projects sponsored by the country’s Department of Corrections and the Aurum Institute, notes that many prison staff supported greater testing, treatment and infection control because of concerns over their own health.
“Prisons are not isolated from the community,” says Hariga. “You have people working in [them], you have prisoners moving in and out very often.”
But despite dismal health statistics, effective penal reform that includes increasing health services for prisoners is far from a reality. Dr. Hariga claims that “there is a lack of interest” among policy makers, resulting in a shortage of funds to address health problems for prisoners. “In many places in the world, there is no health-in-prison programme,” she states.
The difficult nature of prison populations also contributes to the low number of programmes. Dr. Charalambous cited logistical concerns that hampered the testing and treatment of prisoners in the South Africa study, who are often moved from prison to prison or released, interrupting HIV and TB follow-up and treatment.
In large part due to this mobility, 21% of patients initiated onto ART within one of the study’s programmes were lost. In another prison, seven of the 22 prisoners who were called for follow-up had been transferred prior to undergoing review.
In order to combat low programme retention, the ongoing study only enrolls prisoners with a sentence of four months or longer. Researchers also “tag” those enrolled, alerting prison authorities not to transfer them unless essential for trial purposes.
Additionally, using symptom-based diagnosis to identify possible TB patients is difficult among prison populations. In the South Africa study, 46% of patients demonstrated any symptom for TB, while 37% displayed a trio of symptoms.
However, Charalambous surmises that some of these can be attributed to the prison environment in general rather than TB infection specifically, and therefore states, “symptom screening might not be as effective in this environment.”
Despite these challenges, Dr. Charalambous is hopeful that prisoners present a captive audience for TB and HIV testing and treatment. Her study suggests that prisoners may be responsive to such programmes: in one site, 98% of prisoners agreed to join. Dr. Reid agrees, claiming that prisons offer unique opportunities for treating marginalised populations.
In order to encourage more prison health programmes, Dr. Reid calls for further research that assesses the rate of acquiring HIV and TB behind prison bars: while data that demonstrates the high rate of both infections among prison populations is readily available, numbers that point to prisons as conducive to their spread is harder to find.
In order to fuel political will, Reid condones the “advocacy, naming and shaming” of countries who boost some of the worst indicators for prisons with regards to overcrowding, HIV and TB, and human rights violations. “Global reporting is essential to get countries to take this seriously,” he says.
References
Charalambous, S. TB-HIV in prisons and the community response: the case of South Africa. Presented at the 40th Union World Conference on Lung Health, 2009.
Hariga, F. Access to HIV and TB services in prison setting, injecting drug users in prisons: myths and realities. Presented at the 40th Union World Conference on Lung Health, 2009.
Reid, A. Guidelines and advocacy: HIV/TB, prisons, IDU and poverty. Presented at the 40th Union World Conference on Lung Health, 2009.
UNAIDS, WHO and Stop TB team up to create TB and Human Rights Task Force
By Mara Kardas-Nelson
In an effort to better coordinate the work of UN agencies and partners, and in recognition of the human rights component of TB and related illnesses, UNAIDS, the WHO and the Stop TB Partnership are in the process of creating a TB and Human Rights Task Force.
The Task Force, currently in the planning stages, will aim to promote a “rights-based approach” to the illness and strategise on how to best protect the human rights of those most vulnerable to and impacted by tuberculosis infection.
The WHO’s Diana Weil, speaking on behalf of the group, says the idea stemmed from a 2001 Stop TB forum which highlighted the potential threat to and protection of rights for vulnerable groups, including women, migrants, prisoners, refugees, and those living with HIV.
Since that time, however, other issues with regards to TB and human rights have emerged, perhaps most prominently MDR-TB.
“Recently, we’ve seen a lot of questions concerning the rights of individuals” says Weil, pointing to cases in South Africa where people “diagnosed with MDR-TB were being detained.”
Such methods “did not address the needs of those patients. They didn’t have proper facilities, access to due process, and it wasn’t clear why they were being isolated or for how long, and what would happen in terms of access to treatment.”
Weil continues: “With the new…government they’ve said ‘we want community-based treatment and community based options.’ People may need to be hospitalized if they get ill…but that should be for the most limited period of time possible.”
The Task Force is concerned with protecting both the rights of TB patients, as well as those vulnerable to TB infection.
“How do you protect the rights of as many people possible from infection, as well as those who are ill?" asks Daina Weil. "We believe in the right to the protection from the risks to health,” which includes access fulfilling the right to adequate housing, food, water, and health care.
In order to comprehensively address human rights for all vulnerable populations, the Task Force will aim to include broad representation from across the world. At a planning meeting for the group that took place in preparation for the 40th Union World Conference on Lung Health last week, “various stakeholders from as may communities as we could [get] together…discussed what should be the aim of this task force, who should participate, and the key objectives that we want.”
While there is already a plethora of work being done on human rights and illness, coordination between such efforts is needed. Groups interested in specific constituencies, such as those that work with prisoners and migrants, are also already involved with the intersection of human rights and health.
But while many agencies and organizations are already “working in very close groups…we want to look at how we can make it bigger” and specifically “harmonise the work that’s been done on TB, HIV and human rights amongst UN agencies.” Weil highlights UNAIDS work on rights and responsibilities of states with regards to HIV as an example of a potential direction for the group.
While the Task Force is still in its infancy, Weil says the team hopes to “put together a policy framework…that would lay out what is a rights based approaches. But more important is a strategic agenda of what partners could do to respond to the issues and problems. We don’t just want to do a problem statement.”
“We want to enhance rights and the application of rights,” she continues. “This isn’t about maintaining the status quo, but enhancing the understanding of human rights approach.” Weil says the group also hopes to tackle legal issues through legislative documents that could help to identify and rectify so-called public health laws that restrict human rights.
Sources
“Stop TB Partnership TB and Human Rights Task Force to Advance a Rights-Based Approach to TB Prevention, Care and Control: Draft Terms of Reference.” 2009.
Weil, D. Personal interview, recorded at 40th Union World Conference on Lung Health, 2009.
Global Fund predicts funding shortages for MDR-TB, asks donors to fulfill their commitments
By Mara Kardas-Nelson
Despite increases in funding for some U.S. global health programmes, the world faces a “huge gap” for HIV, TB and malaria funding, especially with regards to MDR-TB, with some countries pegged to lose much of their international financial support in the coming months.
Dr. Amy Bloom of USAID told delegates of the 40th Union World Conference on Lung Health, which took place in Cancun, Mexico, “this is a very exciting time for those of us in the U.S. government. Over the last few years we’ve seen an increase in our funding, especially for PEPFAR, our malaria fund and TB funding, but now we’ve entered a phase where we’ve reached a much more holistic approach as well.”
Bloom is especially optimistic about President Obama’s recently announced Global Health Initiative, which could offer up to $63 billion towards global health programmes over the next six years.
She claims that this initiative, coupled with an increase in funding and expanded mandate of PEPFAR, will allow for general health systems strengthening with a focus on HIV and TB integration.
While initially created primarily as an “emergency response,” PEPFAR is now broadening its mandate to include other health issues. TB, for example, is now a “priority area for PEPFAR programme work,” says Bloom.
Over the last decade tuberculosis programmes have seen an enormous increase in funding from the US government, going from no money allocated in 1998 to $176 million allotted for 2009.
Despite this, the Global Fund’s Dr. Rifat Atun warns that without continued commitment and increased funding, the progress made could be easily lost. “Next year is our replenishment year,” he says, “and it’s very important that the level of funding…not just be on par with what we’ve received from funders in the past, but go beyond for further scale-up.”
The bulk of US government and Global Fund money goes to sub-Saharan Africa and Southeast Asia, epicenters of the HIV and TB epidemics. Partially as a result, Eastern Europe and Latin America and the Caribbean—areas that have less generalised epidemics but still face large burdens of disease—are strapped for cash.
The funding situation for Eastern Europe is especially worrisome to Atun, as many countries in the region face high rates of MDR-TB but will soon be ineligible for Global Fund money as their status changes from “low-income” to “middle-income.” This change, however, is unlikely to be met with an increase in domestic funding, and programmes are predicted to face an even larger financial shortfall.
“Many countries with high MDR-TB, especially within Europe, will not be eligible for the Global Fund but need external funding,” he explains. While USAID efforts are increasing in the region, the money allocated is still “quite small,” adds Bloom.
According to Atun, “there’s no one to pick up this shortfall…It’s unlikely that we will find money [for the gap].” Many Latin American countries will also soon face exclusion from Global Fund grants.
“No one has really thought about this issue,” says Atun. “It’s a big problem. There’s no earmarked funding, and if we begin to think about it now, it will take two to three years to get this in place.”
On a global scale, Atun is encouraged by the increase in applications for TB grants during Round 9 of Global Fund funding. “For the first time the TB community has joined the ‘billion dollar club,’” he says, referring to the amount of money allotted for diseases. “That’s very good news.
“The best performing grants in our portfolio are TB grants,” he continues. “The TB community is doing something right. For Round 9, the applications have been less formulaic and more ambitious…particularly in relation to TB and HIV, [with] some thinking about integration with health systems.”
Atun encourages more TB-focused Global Fund proposals, as well as more advocacy and research into the economics of TB treatment and care. “It’s very important…that the TB community is not left behind,” he says.
References
Atun, R. Updates on current donor mandates and means of supporting scale-up in countries: Global Fund. Presented at the 40th Union World Conference on Lung Health, 2009.
Bloom, A. Updates on current donor mandates and means of supporting scale-up in countries: USAID. Presented at the 40th Union World Conference on Lung Health, 2009.
TB world looking to successes of HIV advocacy to guide renewed efforts
By Mara Kardas-Nelson
In order to garner more media attention, funds and political commitment for tuberculosis, scientists, policy-makers and advocates are looking to the successes of the HIV movement to help guide a powerful patient-driven approach to lung health.
Throughout the weekend-long the 40th Union World Conference on Lung Health that took place in Cancun, Mexico, speakers and delegates pointed to the advocacy and activism of the AIDS movement and its effects on domestic and international investment in combating the virus.
While tuberculosis has plagued humanity for much longer than its viral counterpart, and claimed a near-equal number of lives over the last 30 years, media attention, policy concentrations, and funding efforts have been lacklustre in comparison to the robust reaction to HIV.
“HIV has been very effective at mainstreaming [the virus] across the development community, and TB…has many of the same characteristics…in terms of how it affects society,” says Diana Weil of the WHO. “So the question is how can we get similar responses…and draw on the lessons of the HIV community.”
According to David Gold of Global Health Strategies, the relatively small TB response is demonstrated primarily through scant funding and minimal media attention. In 2008, for example, the Global Fund granted $327 million for TB, or 11% of its total funding, with the rest going to malaria and HIV. During the same time, HIV and TB claimed nearly 2 million lives each.
Media coverage is equally disproportionate with regards to the effects of TB. Gapminder assessed the frequency of news reports regarding swine flu and tuberculosis respectively from 24 April to 6 May 2009. During this time 31 people died of swine flu, with 253,442 reports being written about the virus, while 63,066 people died of tuberculosis, with only 6,501 news reports mentioning the disease. The news-to-death ratio based on these findings is 8176:1 for H1N1, and 0.1:1 for tuberculosis.
A Global Health Solutions analysis of TB in the media, assessing news reports from August 2006-April 2009, found that the majority of tuberculosis-focused articles were written during World TB Day or international lung conferences, often focusing on drug access and research, and diagnostics.
The 2007 Andrew Speaker XDR-TB incident, during which an American drug-resistant TB patient flew transatlantic against medical advice, potentially infecting his fellow passengers and thereby their communities, also made headlines throughout North America, Europe and South Africa.
Generally, reporters focused more on MDR- or XDR-TB than non-drug resistant strains. As is the case with funding, malaria and HIV outshone tuberculosis coverage.
Gold suggests that media is an important component to advocacy and activism, and was essential to the strong HIV response. Media coverage increases awareness and can help to disseminate important public health messages regarding prevention, testing, treatment and care.
Gold notes that the 2000 Durban International AIDS Conference helped to bring the world’s attention to the virus, particularly by highlighting a patient perspective and bringing together often disparate groups, such as affected communities, advocates, funders, and policymakers.
Patient advocacy and involvement is most important to the strength of the HIV response, Gold continues. While “TB is considered a public health control issue led by health care professionals rather than activists,” there are more opportunities, including paid work, for patients and patient advocates within the HIV/AIDS sector.
In comparison with TB organisations, there is “greater incorporation of patients into all aspects of AIDS organisations, including governance,” he says.
Dr. Bertel Squire, president of the International Union Against Tuberculosis and Lung Disease, agrees, claiming that the “inclusion and participation by persons affected by lung disease across all levels of all endeavours,” coupled with “permanent…funding” is necessary to “sustain and increase our efforts.”
Gold sees the 2007 Speaker incident as a “lost opportunity” in which the global TB community could have used the case to highlight the threat of drug-resistant tuberculosis, the need for better diagnostics and treatment, and the incidence of TB even in wealthy, industrialized nations like the United States.
Instead, Gold contends, the case was “shunned and rejected by the TB community,” with Speaker not being encouraged to tell his story, thereby foregoing the chance to engage a patient advocate.
In order to make TB better represented, Gold suggests forging a stronger connection between activists in the global North and South, and “[focusing] on moral issues and patient rights in terms of the fight for better drugs, diagnostics…and stock outs.”
High burden countries such as India and South Africa should also act as leaders in the fight against the bacterium, in the same way that Brazil, Thailand, Botswana and Uganda responded urgently and innovatively to the HIV epidemic.
Reference
Gold, D. TB Advocacy and mass media: what can we learn from the HIV community? Presented at the 40th Union World Conference on Lung Health, 2009.