Islands of Hope: Building Local Capacity to Manage an Outbreak of Multidrug-Resistant Tuberculosis in the Pacific

Abstract

A single case of multidrug-resistant tuberculosis (MDR-TB) can overwhelm the technical and financial capacity of small TB programs. In May 2008, the island state of Chuuk requested assistance for their first cases of MDR-TB. Second-line drugs and isolation rooms were unavailable, lab capacity was limited, and clinicians lacked experience. Delayed response caused prolonged transmission among household contacts.

Several agencies responded with technical assistance and resources. Subsequent evaluations identified 16 additional MDR-TB cases and 124 infected contacts. Within six months, the local TB program gained remarkable capacity to manage MDR-TB cases and contacts, and greatly improve care for all TB patients. The Chuuk outbreak demonstrates the importance of establishing MDR-TB readiness in smaller jurisdictions and maintaining an essential TB control infrastructure.

TUBERCULOSIS (TB) IS THE second leading cause of death from infectious disease in the world and remains a major public health problem throughout the Pacific basin.^1a Further exacerbating the global TB problem is the continuing emergence of multidrug-resistant (MDR) TB. Higher morbidity and mortality rates occur with MDR-TB than with drug-susceptible TB. MDR-TB is resistant to treatment with isoniazid and rifampin—the two most potent first-line TB drugs.^1b

Diagnosis and treatment of MDR-TB in endemic areas is a relatively new public health challenge. Successful response requires isolation of infectious patients, rapid procurement of and treatment with second-line medications, and consistent directly observed therapy (DOT). On a global scale, many rural communities do not have adequate resources or the expertise needed to address this daunting public health problem.

The Federated States of Micronesia is a US-affiliated jurisdiction that comprises more than 600 islands dotted across 1 million square miles in the western Pacific Ocean. Micronesia is a low-income country where 27% of the people live below the US poverty line.² While TB incidence in the United States continues to drop (4.4 reported cases per 100 000 population in 2007), Micronesia has sustained some of the highest rates of TB among the US-affiliated Pacific Islands (169 reported cases per 100 000 in 2008).³

Chuuk is the largest Micronesia state with a population of 55 000 people. The average household has seven people, but it is not uncommon for more than 20 family members to sleep within a single dwelling. Approximately 30% of Chuuk's population lives on the main lagoon island of Weno, which has the state's only hospital. Access to health care is limited by geographic distance and minimal staffing. The local Ministry of Health provides basic health care services to those living on outer islands, because some population centers are accessible only by health care staff braving two days at sea. All diagnostic evaluations, including x-ray and lab services, are limited to Weno. At the time of the MDR-TB outbreak, the TB control program consisted of only two nurses and one part-time clinician.

Chuuk State receives programmatic funding for TB control from the United States as well as from the World Health Organization's (WHO) Global Fund to Fight AIDS, Tuberculosis, and Malaria. With limited assistance and few local resources, it was difficult for the Chuuk TB program to implement core elements of TB control. Rather than seeking out active cases, TB patients were usually identified as they arrived at the hospital with the disease. As in many other countries, second-line drugs for treating MDR-TB were not available.¹

Without essential DOT, all TB cases administered their own therapy. The hospital lacked an isolation ward and infectious TB cases were treated in open-air general wards. Without a public health laboratory, timely TB culture confirmation, drug-susceptibility testing, and genotyping were difficult to obtain. Finally, as in many small countries, Chuuk did not have a radiologist, an infectious disease specialist, or any other clinician with experience treating MDR-TB.

OUTBREAK PRESENTATION

In June 2007, pulmonary TB was diagnosed in an adult, HIV-negative, Chuukese male. Treatment of presumed drug-susceptible TB began, without clinical improvement. In November 2007, drug-susceptibility test results from a regional TB reference laboratory confirmed multidrug resistance. The Chuuk TB control program was unable to procure second-line drugs, and the patient died. Between December 2007 and June 2008, four additional patients infected with MDR-TB were seen at the local hospital. Still without access to second-line drugs, three died, including a mother and two-year-old child, leaving just one surviving case. Significantly, all five patients with MDR-TB disease had prolonged infectious periods of untreated illness and extensive household contacts.⁴

MULTI-AGENCY INVESTIGATION AND RESPONSE

At the request of the Micronesia government, a team comprised of representatives from the Centers for Disease Control and Prevention (CDC), WHO, and the nearby Commonwealth of the Northern Mariana Islands arrived in July 2008 to investigate the deaths from MDR-TB.⁴ In addition to the initial five cases, 16 other MDR-TB cases were subsequently identified during the period July 2008 through May 2009, including a four-year-old household contact who died of MDR-TB meningitis in November 2008. The contact investigations for these cases evaluated 205 close contacts. Among the MDR-TB contacts, 124 (60%) had positive tuberculin skin test results consistent with latent TB infection.⁴ HIV tests were ordered on every case and contact. No cases or contacts are known to be HIV infected.

The multiagency team worked with local program staff to create a plan guided by the WHO Global Response Plan for Drug-Resistant TB.¹ The plan included several key components which addressed program capacity needs. First, DOT had to be established for all TB cases to ensure complete treatment and prevent further development of TB resistance. Second, an isolation facility was required to safely treat cases of MDR-TB. Third, adequate supplies of second-line drugs needed to be procured. Finally, community education was needed to reduce the stigma of TB and remove some of the social barriers to care.

With funds from the Micronesia national government and US Department of the Interior, an adequate supply of second-line TB drugs was immediately purchased. These medications were selected in consultation with CDC experts. As a major program accomplishment, local access to national and international subject-matter experts was greatly enhanced.

Chuuk lacked the infrastructure and experience required to deliver daily intravenous medication outside of the hospital. In August 2008, a temporary MDR-TB isolation unit was constructed in an abandoned area of the hospital; local breezes and electric window fans were used to create a negative-flow environment. Initially six patients, five of whom were children, were identified for inpatient treatment. By January 2009, 10 additional cases were diagnosed and included in the MDR-TB cohort.

Current CDC and WHO standards for treatment for a typical case of MDR-TB recommend 6–9 months of intravenous therapy along with 18–24 months of oral second-line drugs. Understandably, families were reluctant to commit to a nine-month hospital-based care regimen. To address family concerns, the community constructed a traditional open-air meeting house adjacent to the isolation ward. The Australian Respiratory Council provided funding for a local schoolteacher, and classes were held in the meeting house during the nine months of hospitalization. Donations from the nearby Commonwealth of the Northern Mariana Islands and from Hawaii helped create a positive living environment for the MDR-TB patients and their families. Several authors have documented the importance of a patient-centered approach toward achieving compliance with difficult TB treatment regimens.^5,6 In Chuuk, these family-centered services contributed greatly toward treatment adherence and were key to the eventual clinical success. Table 1 lists several of the agencies contributing to the outbreak response.

TABLE 1.

Agencies Providing International Assistance for Multidrug-Resistant Tuberculosis Epidemic: Chuuk, Federated States of Micronesia, 2008-2009

Agency	Type of Assistance	Purpose
Centers for Disease Control and Prevention	Technical	Outbreak evaluation
	Technical	Directly observed therapy training
	Technical	Treatment supervision
	Technical	Contact evaluation
	Financial	Tuberculosis cooperative agreement
World Health Organization	Technical	Outbreak evaluation
	Technical	Directly observed therapy training
	Technical	Contact evaluation
	Financial	Global fund resources
Secretariat of the Pacific Community	Technical	Outbreak evaluation
	Technical	Directly observed therapy training
Federated States of Micronesia	Technical	Directly observed therapy training
	Financial	Grants management
Commonwealth of the Northern Mariana Islands	Technical	Outbreak evaluation
	Technical	Treatment supervision
	Technical	Directly observed therapy training
	Technical	Contact evaluation
	Financial	Family donations
	Financial	Equipment donations
US Department of the Interior	Financial	Compact impact funds
	Technical	Financial oversight
US Department of Defense	Technical	Contact evaluation
ReachOut Pacific	Financial	Family donations
Australian Respiratory Council	Financial	Tutoring project

Sustainable tuberculosis program improvements were needed for the community as well. By September 2008, 10 new community workers were hired and began DOT training, consistent with CDC and WHO standards.^7,8 By late September, three trucks were purchased to allow for daily treatment of drug-sensitive TB cases and MDR-TB contacts in the local villages.

In October 2008, strict DOT was instituted in Chuuk, and it had an immediate and profound effect on local TB control. The total number of cases identified in the community (including non-MDR) increased sharply from 30 cases in September 2008 to 93 cases in January 2009. In May 2009, nine more community workers were hired to extend DOT to the most remote villages and outer islands. Before the MDR-TB outbreak, the Chuuk program was unable to sustain DOT service to any patients. Within six months, the program developed remarkable capacity to deliver TB medications to more than 180 cases and contacts every day.

DISCUSSION

In Chuuk, the discovery of MDR-TB overwhelmed the existing capacity of the local public health department and led local officials to declare a state of emergency. The outbreak of MDR-TB was facilitated by the use of self-administered therapy and poor monitoring of adherence, limited isolation procedures and infection control practices in health care settings, limited access to health care services because of transportation challenges and remoteness of populations, lack of active case finding through contact investigations, and limited outreach for patient education.

Nevertheless, the most important factor contributing to the transmission of MDR-TB was delayed access to effective second-line medications, which resulted in prolonged infectious periods. Beginning in December 2007, several efforts to obtain second-line medications were unsuccessful. More than 1 year passed between the first recognized MDR-TB case and the arrival of second-line medications. Much of the delay was caused by inadequate local finances. The direct medical cost of MDR-TB in the United States can be as much as $137 000 per case, not including associated contact investigation costs.⁸ In small countries like Micronesia, where the annual TB control budget is US $170 000, a single MDR-TB case can easily overwhelm local resources.

Appropriately, resources and technical assistance from outside agencies facilitated remarkable and sustainable advancements by the local TB control program. Within six months, all patients with active TB disease were treated with DOT, a reconstructed 18-bed isolation ward was created, second-line therapy was procured for all patients with MDR-TB disease or latent MDR-TB infection, and contact investigations were conducted on all newly identified smear-positive patients. Furthermore, an additional public health physician, 5 nurses, and 18 DOT workers were hired, and TB program staff members now regularly engage in educational sessions for the public about TB disease, treatment, and prevention. A particularly noteworthy accomplishment is that in the 12 months following implementation of these programmatic improvements, TB mortality in Chuuk dropped from 11% of all TB cases to less than 1% (US mortality rate is 5%), despite a significant increase in the number and complexity of treated cases. Figures 1 and 2 displays the remarkable program improvements demonstrated by the Chuuk TB program.

FIGURE 1.

MDR-TB outbreak in Chuuk, Federated States of Micronesia.

Note. CDC=Center for Disease Control and Prevention; DOT=directly observed therapy; MDR=multidrug resistant; TB=tuberculosis.

FIGURE 2.

TB survival during treatment improved dramatically for all cases after establishment of community-based DOT.

Note. DOT=directly observed therapy.

FIGURE 3.

Effective, life-saving second-line drugs were not obtained for more than one year after the first case was identified, resulting in a larger number of secondary cases. Photo by S. Bamrah.

FIGURE 4.

An isolation and treatment facility was constructed to manage the cases. More than half of the MDR-TB outbreak cases were in children. Photo by R. Brostrom.

Many of these program improvements were funded by the US Department of the Interior, through prior unused funds originally granted to Micronesia. However, this outbreak prompted the program to reprioritize local resources for the growing TB problem. To ensure sustainability, many program enhancements have already been absorbed by the local budget, including DOT worker salaries and inpatient care costs for MDR cases. Other improvements, including remodeling costs and the purchase of digital x-ray technology, vehicles, and most of the second-line drug supplies, were one-time expenditures that will improve local capacity for years to come.

CONCLUSIONS

MDR-TB is a growing challenge to all regions of the world. TB control programs that are not achieving basic standards can create MDR-TB cases because of inadequate DOT. These same programs will likely have a difficult time managing the costs of treating MDR-TB cases. Small TB programs may struggle to manage outbreaks in a timely manner. Avoidable delays in Chuuk resulted in the surprisingly rapid expansion of infectious cases and contacts with latent MDR-TB disease, which caused the potential for MDR-TB to be firmly entrenched in the community for many years.

To prevent the unnecessary spread of this costly disease, vulnerable TB programs must undertake programmatic improvements to effectively manage the threat of MDR-TB. Regional partners with experienced consultants should work to ensure adequate local capacity for MDR- TB management prior to the arrival of the first case. Rapid access to second-line drugs must be ensured for all programs to prevent the spread of drug-resistant TB and directly observed therapy must be utilized for all TB cases to prevent the development of drug resistance. Safe isolation and treatment facilities should be available to TB programs, and access to quality laboratory services for culture and drug-susceptibility testing must be ensured. Additionally, clinical and programmatic training should be available for all TB control programs. To prevent a local public health crisis, smaller programs must achieve these fundamental TB control strategies before the arrival of their first MDR case.