Open access peer-reviewed chapter

Loss to Follow-Up (LTFU) during Tuberculosis Treatment

Written By

Kyaw San Lin

Submitted: May 25th, 2018 Reviewed: October 8th, 2018 Published: September 16th, 2019

DOI: 10.5772/intechopen.81900

From the Edited Volume

Healthcare Access

Edited by Umar Bacha, Urška Rozman and Sonja Šostar Turk

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Abstract

Loss to follow-up (LTFU) is a serious issue in the field of tuberculosis (TB) since it can lead to TB outbreaks and drug resistance. The proportion of LTFU patients differs among different countries, regions, year, and institutions. In some countries, the number of patients that were LTFU nearly reaches half of the total patients. Underlying factors such as age, gender, education, residence, financial factors, migration, and social stigma are discussed in this chapter. These factors should always be taken into consideration whenever a treatment program is designed. Suggestions have been made regarding some interventions that could potentially solve the problem of LTFU. With these points in mind, an ambitious approach should be taken to reduce the number of LTFU patients up to zero.

Keywords

  • tuberculosis
  • TB
  • loss to follow-up
  • LTFU
  • default

1. Introduction

Tuberculosis (TB) is a disease, which requires more than just biomedical treatment. WHO-recommended standard TB treatment requires a minimum duration of 6 months. The patients have to regularly take treatment without interruption to get a cure. However, discontinuation of treatment because of loss to follow-up (LTFU) is a significant problem, especially among patients suffering from multidrug-resistant tuberculosis (MDR-TB), requiring urgent attention. The proportions of LTFU and its associated factors differ among various countries. A clear understanding of these underlying causes is essential for the success and effectiveness of the National Tuberculosis Program (NTP) of every nation. Hence, appropriate measures targeting LTFU are needed to achieve the goals of the NTP.

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2. Definition

In 2012, a large group of researchers from Africa, Asia, America, Europe, and the Pacific suggested that the term ‘defaulter’ is inappropriate for the patient [1]. Instead, they recommended using the term ‘person lost to follow-up’ to become more patient-centered. In 2013, the WHO decided to use the term ‘loss to follow-up’ instead of ‘defaulter’ for reporting treatment outcomes because the former is less judgmental [2]. They defined LTFU as “A TB patient who did not start treatment or whose treatment was interrupted for 2 consecutive months or more.” Since then, several papers have started reporting according to this new term and definition [3, 4, 5, 6, 7, 8, 9, 10].

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3. The problem of LTFU

The patients who were LTFU have not completed the treatment regime. This can cause serious public health problems because these patients are at higher risk of drug resistance [11]. They continue to spread the potentially resistant bacilli to the public, infecting the public. This has been proved in a Bayesian mapping where LTFU has served as an important indicator for the distribution of TB patients [12]. Therefore, LTFU should be one of our primary concerns in the battle against TB.

Even just a single case of LTFU could cause an outbreak of TB, as observed in countries with low incidence such as Norway [13, 14], USA [15], and Austria [16]. In such outbreaks, the index cases are mostly immigrants, spreading the infection to their families, friends, and other social networks. To further visualize this problem, we need to look into the proportion of LTFU among different countries in the world.

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4. Proportion of LTFU

The proportion of LTFU varies considerably among different countries, different types of TB, and different patient populations. It has been studied extensively and was found to be ranging from 2.5 to 44.9% [17, 18, 19, 20, 21, 22, 23]. A very high proportion (44.9%) of the patients were LTFU in rural northern Mozambique revealing that LTFU is a very serious problem [19]. In addition, systematic reviews and meta-analyses have estimated the mean proportion of multidrug-resistant TB patients who were LTFU. A 2009 systematic review of MDR-TB patients has found that this proportion is 12% [24]. Another 2009 systematic review also found a similar proportion of 13% [25]. However, a 2012 individual patient data meta-analysis found a higher proportion of 23% [26]. A rough literature review has revealed that the proportion of MDR TB patients who were LTFU ranges from 2.2 to 47% [27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43]. The figures vary vastly among different years, countries, and institutions, suggesting that the underlying factors responsible for these variations should be studied carefully.

However, few studies have reported on the proportion of LTFU among patients with extra-pulmonary TB. According to a French study, this proportion was 25% among lymph node TB patients [44]. Another study from Gabon reported that the proportion among cervical lymph node TB patients was 24.3% [45]. In India, among the miliary tuberculosis patients presenting with neurological manifestations, the proportion was 10% [46]. However, in Saudi Arabia, the proportion among CNS tuberculoma patients was reported to be 25.8% [47].

Another area of interest is latent TB since developed countries such as the USA and the UK are giving much attention to latent TB and its LTFU rate. Studies from the USA reported proportions ranging from 12 to 35.6% [48, 49]. In the UK, this proportion is 22.8% [50], and in Switzerland, 11% [51].

Attention should also be paid toward LTFU among certain special populations. The proportion of LTFU among childhood TB patients ranges from 4 to 37% [52, 53, 54, 55, 56, 57]. Among the children with drug-resistant TB, it ranges from 5 to 19.09% [58, 59, 60]. These figures are much similar to those of the adult population. On the other hand, researchers from Côte d’Ivoire found out that the proportion of LTFU was rising among the elderly TB patients [61]. This is an area that researchers should explore more in the future.

We should not forget about our fellow healthcare workers since LTFU could lead to serious problems in the healthcare service setting. They are expected to have low rates of LTFU because of the medical knowledge they possess. Fortunately, a study from Morocco confirmed that the proportion of LTFU among healthcare workers in the public sector was only 0.8% [62]. However, many studies need to be done to explore this area of study.

Other populations of interest are prisoners and migrants. Northern Ethiopian prisons reported a low LTFU proportion of only 2.5% [63], which is an excellent result. In contrast, among the Ugandan prison inmates, 43% were LTFU and the odds are greater among the transferred prisoners [64]. On the other hand, researchers from the USA found out that 25.8% of the cases in a public health intervention were LTFU, and they were mainly undocumented migrants [65]. In such countries, as discussed above, even a single case of LTFU can cause an outbreak of TB. The same problem is arising in Australia where all of the detained illegal foreign fishermen were LTFU [66]. They concluded that

“Treatment completion in illegal foreign fishermen may be as low as zero; deporting fishermen before curative treatment is completed undermines TB control efforts and may lead to an emergence of drug resistance and an increased burden of active TB disease in our region.”

This is an area of concern that needs urgent measures. On the other hand, the International Organization of Migration is achieving great results among Vietnamese immigrants [67]. Only 7% of the MDR-TB patients from these migrants were LTFU. It is likely that such ‘international intergovernmental’ effort is necessary to tackle the problem of LTFU among the migrants since individual governments are facing difficulties handling this problem.

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5. Factors associated with LTFU

5.1 Individual factors

Individual factors play a role in the process of being LTFU from treatment. Sometimes, the results may contradict between different studies, probably due to the cultural, social, and other variations of the study settings.

Among the various sociodemographic characteristics, age is a recognized factor associated with LTFU. Studies from India, Brazil, and China revealed that elderly patients have higher LTFU [4, 68, 69, 70], whereas studies from Norway, Botswana, and South Africa suggested that adolescents have significant risk [8, 30, 71]. One study from the UK even suggested a wider range of age of 15–44 years as a high-risk group for LTFU [11]. Regarding gender, studies uniformly suggest that higher LTFU was found in males, as seen in Kenya, Ethiopia, Georgia, and Uzbekistan [7, 18, 41, 72].

Residence plays a role in the mechanism of LTFU. In Pakistan, the rural residence is associated with LTFU [73], whereas in Uzbekistan, the urban residence is associated with LTFU [18]. This may be caused by access to the treatment center since being far from the treatment center is also associated with LTFU [74]. Transportation should be improved to increase accessibility toward the treatment center. Alternatively, they could be built in the hard-to-reach areas. Both approaches include challenges, and ultimately, these challenges may be what cause LTFU. Further discussion regarding different providers will be given in the next section.

Education plays a role in the development of LTFU. Brazilian researchers have found out that less than 8 years of schooling increases the risk of LTFU [4]. In addition, scarce TB knowledge is a risk factor for LTFU [75], and better TB knowledge a protective factor [5]. Therefore, health education and proper counseling should always be at the heart of every anti-TB treatment program.

Financial factors should also be considered while giving treatment, and programs without such considerations will likely to result in high LTFU. A study from Uzbekistan found that joblessness contributes toward LTFU [18]. This is confirmed by a study from China which found that pre-school children, unemployed laborers, and retirees have a higher rate of LTFU [76]. Patients with low income have financial constraints to complete treatment leading to LTFU as seen in India [77], a lower middle-income country. A similar phenomenon has been observed in South Korea, a high-income country [78]. Even in the USA, it was found that homelessness is associated with LTFU [79, 80], which might be due to low income. Therefore, regardless of the country, patients with low income still have barriers against treatment completion.

LTFU is also associated with alcohol abuse, tobacco use, smoking, and illicit drug use. Association between alcoholism and LTFU was observed in India [77], Philippines [5], and Congo [74], tobacco use in Georgia [41], smoking in Brazil [75], and illicit drug use in Norway [30], Georgia [41], and the UK [81]. Therefore, before initiating treatment, personal history should be carefully taken to find out these risk factors, and special attention should be given to such patients.

There are also certain disease-specific factors that are associated with LTFU. Those who were previously LTFU tend to be LTFU again. This was confirmed by studies conducted in Brazil [4], Kenya [7], Uzbekistan [18], and Korea [78]. Caution should be taken while planning treatment for such patients. Studies from Nigeria and Ethiopia both point out that smear-negative TB patients were more likely to be LTFU [72, 82]. However, the opposite was observed in the UK where smear-positive pulmonary TB patients were more likely to be LTFU [11]. Researchers also found that patients with extrapulmonary TB were more likely to be LTFU [71, 83]. Co-morbid diseases such as diabetes mellitus and human immunodeficiency virus (HIV) infection also cause hindrance against TB treatment conditions [7, 71, 84].

5.2 Treatment support services

The treatment providers should give support to the patients since a perceived lack of provider support is a barrier to regular follow-up [77], and receiving any type of assistance and support from the providers can protect against LTFU [5]. They need to build up trust [5] from the patients. An intervention program targeting these factors will be described later in the chapter. Lastly, the timing of the treatment services should be flexible according to the needs of the patients [77], but this may not be an easy task to implement.

5.3 Diagnosis and treatment

The timing of the treatment is important since those who initiate the treatment late (beyond and within 30 days of onset) are more likely to be LTFU [85]. Those who initiate it late may not have enough motivation, will, or knowledge to continue taking treatment until they are cured. Moreover, the timing of treatment interruption is found to be the most important during the intensive phase [7]. This stage should be particularly targeted while conducting interventions against LTFU.

Different providers have different abilities to retain the patients. In Korea, patients treated by a non-pulmonologist were found to be more likely to default from TB treatment [78]. In Myanmar, patients treated by private practitioners were more likely to be LTFU [86]. An interesting situation was observed in Nigeria where patients treated at private, not-for-profit (PNFP) DOT facilities were more likely to be LTFU [87]. The researchers concluded that “Patients managed at PFP [private, for-profit] DOT facilities were probably richer, had better education, nutrition, and knowledge of TB than patients managed at PNFP DOT facilities…” Indeed, the factors causing LTFU are not simple, and they are correlated with each other. Therefore, intervention should be addressed not only on a single problem but also targeted toward the patient as a whole. Furthermore, the provider should also be consistent throughout the different stages of treatment since different providers in the intensive phase and continuation phase are associated with LTFU [88].

5.4 Drug side effects

Studies from the USA and India have found that drug side effects are associated with LTFU [49, 77]. The researchers from the Philippines take one step further regarding this concept, stating ‘patients’ self-rating of the severity’ as an associated factor [5]. Indeed, some side effects, such as hepatitis, of the anti-tuberculosis drugs are already severe. However, some side effects, such as vomiting, might need self-rating since different patients may perceive differently. It would be interesting to research which kind of patient rates which side effect as severe.

5.5 Social factors

Factors such as migration and social stigma also contribute toward LTFU. LTFU is common among the migrant population particularly in developed countries where there is an inward movement of people from the developing countries. Studies from the UK had repeatedly revealed this association [11, 50, 86, 89]. Researchers from the USA also found that birth outside the USA or Canada is associated with LTFU [80]. Higher LTFU among migrants has also been observed in Asian countries such as South Korea and China [70, 76, 90].

In countries where TB is a social stigma, treatment is very difficult and sensitive [77]. The patients may not want the health workers to give counseling. They do want to take treatment since the news of having TB may spread to the community, causing discrimination. In such places, secret treatment sessions should be initiated to control LTFU rates. In contrast, in Korea, the absence of TB stigma is associated with LTFU [78]. The authors wrote “TB stigma might motivate patients to receive TB treatment, thus increasing adherence to TB treatment.” Therefore, before starting the TB treatment program, it is important to make community observations first to find out whether TB sigma can cause or prevent LTFU.

In theory, interpersonal factors such as family dynamics, household role, peer influence, and partner and family relationships were thought to influence LTFU [5]. However, to our knowledge, none of the studies to date supports the association of LTFU with these factors.

5.6 Scoring instrument

Based on the factors associated with LTFU, Rodrigo et al. have developed a scoring instrument to predict the probability of LTFU (Table 1) [91]. According to their original paper, “Scores of 0, 1, 2, 3, 4 and 5 points were associated with a lost to follow-up probability of 2.2% 5.4% 9.9%, 16.4%, 15%, and 28%, respectively.” Incorporating the instrument in the process of history taking could help the healthcare providers in identifying patients who have the potential to be LTFU. Further interventions should be carried out to prevent these patients from becoming LTFU. Similar scoring systems could be developed in different regions, since there are always country-specific variations.

LTFU riskScore
Immigration1
Living alone1
Living in an institution2
Previous anti-TB treatment2
Poor patient understanding2
Intravenous drug use (IDU)4
Unknown IDU status1

Table 1.

A predictive scoring instrument for tuberculosis lost to follow-up outcome [86].

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6. Interventions

6.1 Directly observed treatment (DOT)

Indeed, DOT is a part of the WHO-recommended ‘Directly Observed Treatment Short Course’ (DOTS) strategy. Although it cannot be denied that this strategy has saved the lives of millions of TB patients, the strategy itself is not flawless. Several authors have questioned the effectiveness of DOT as summarized in a review article by Otu [92]. The 2015 Cochrane systematic review and meta-analysis on DOT compared it with self-administered treatment, and the authors concluded that “TB cure and treatment completion were low with self-administered therapy in these trials, and direct observation did not substantially improve this” [93]. They called for complementary and alternative strategies in addition to DOT. Since DOT is a well-known and well-documented intervention in the field of TB, we felt that it need not be described in further detail in this chapter. Some interventions that have the potential to correct the weaknesses of DOT will be discussed below.

6.2 mHealth

Recently, mHealth has emerged as a popular choice for health programs around the world. The Global Observatory for eHealth (GOe) has defined mHealth as “medical and public health practice supported by mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants (PDAs), and other wireless devices” [94]. Among these mHealth initiatives, appointment reminders and treatment compliance initiatives are of interest in reducing the rate of LTFU. However, there are limited interventional studies evaluating the effectiveness of these interventions in reducing the risk of LTFU.

In 2017, Hermans et al. have evaluated a text message service in the Infectious Diseases Institute (IDI) in Kampala, Uganda [95]. In this quasi-experimental study, appointment reminders were sent the day before the appointment, and adherence reminders were sent on days 2, 7, and 11 after the appointment. A total of 96% of the participants rated the messages as being helpful, and qualitative results also confirm these findings. However, data analysis has revealed that there was no statistically significant difference in the risk of LTFU between the intervention and control group. The lack of statistical significance may be due to the small sample size. Therefore, further studies with larger sample sizes are needed to further evaluate the program.

6.3 eCompliance

eCompliance is a biometric-based program, developed by Operation ASHA (OpASHA) [96], an Indian not-for-profit organization founded in 2006. The system is similar to mHealth in using text message alerts to inform the missed dose. However, the unique fingerprint verification system for the patient and the health worker takes mHealth to the next level. The OpASHA website explains the working mechanism of eCompliance as follows.

During each patient visit, the patient and healthcare worker simultaneously scan their finger in the system, the medication is dispensed, and the treatment is recorded in the system’s database. If a patient misses a dose, an SMS message alert is sent to the patient, healthcare worker and supervisor. The healthcare worker is then responsible to meet the patient within 24–48 hours to administer and record the treatment.

This system can be used to reduce the risk of LTFU since the data from OpASHA stated that the LTFU rate is less than 4% using their system [96].

This claim by OpASHA has been put to test in Uganda by Snidal et al. in 2012 [97]. Community health workers (CHWs) were selected and trained to use the system. The intervention was conducted at the Millennium Villages Project (MVP) cluster in Ruhiira, Uganda. The patients were followed-up by CHWs until the end of the treatment period. The proportion of LTFU is surprisingly 0% in the intervention group, which is a significant reduction compared to the control group, yielding an excellent result. However, since this study suffers from a limited sample size, a large-scale interventional study is still necessary to confirm the results. Local adaptation to the software is available from OpASHA, and they should be incorporated into local national tuberculosis programs to lower the proportions of LTFU.

6.4 Community-based programs

An innovative community-based intervention to improve TB treatment outcomes was conducted in Sidama zone, Ethiopia [98, 99]. The core health workers mainly responsible for delivering the intervention to the grass-root level were called the health extension workers (HEWs). The HEWs were trained and salaried female health workers from the respective intervention regions. Active case finding and sputum smear preparation were conducted by the HEWs. The supervisors process the smears and initiate anti-TB treatment. Again, HEWs provide treatment support which includes provision and monitoring of treatment. Evaluation of the program over 4.5 years revealed that the proportion of patients lost to follow-up decreased significantly up to 3% [99]. The authors concluded that

We have thus demonstrated that bringing simple services that detect disease and provide treatment support close to where patients live is critical to increase access to TB diagnosis and treatment adherence and minimise the number of patients LTFU.

Therefore, such community-based programs should be implemented in modified forms in different countries around the world to reduce the proportion of LTFU. Another important thing to note is that both this program and eCompliance mentioned above employed ‘task shifting’ toward basic health workers (CHWs and HEWs) to support TB treatment at the grass-root level, not the experts.

6.5 Social support programs

In 2013, a novel social support program was developed in India by forming groups called “treatment support group (TSG)” [100].

A TSG is a non-statutory body of socially responsible citizens and volunteers to provide social support to each needy TB patient safeguarding his dignity and confidentiality by ensuring access to information, free and quality services and social welfare programs, empowering the patient for making decision to complete the treatment successfully.

A TSG supports the various needs of the patient so that they can complete the anti-TB treatment without any worries. The package includes transportation service, treatment counseling, emotional and spiritual support, and providing accommodation for homeless TB patients. After the program was implemented, the rate of LTFU fell until it strikes zero in the latest cohorts. It is because it tackles the social dimension associated with LTFU. This is one program that the interviewed patients from Ethiopia, who were LTFU, had hoped for [101].

6.6 Legislation

In some countries, under certain circumstances, law enforcement is controversially used to solve the problem of LTFU. Usually, the patients who were LTFU were isolated in hospitals, but in some countries, they were isolated in prisons. Usually, this method was used against patients who were homeless and had a history of alcohol abuse [102]. When all the other methods fail, the medical officer, with the power given by the health laws, has to conduct a short-term incarceration of the patients who were LTFU.

Detention of patients includes ethical and human right problems. The controversy surrounding this issue has been discussed in detail in a review article by Mburu et al. [103]. They discussed that the primary reason for detention is to protect public health, according to the Siracusa Principles adopted by the UN Economic and Social Council. However, they argued that this conflicts with the international human right laws and the 1979 Alma-Ata Declaration.

…incarceration and detention approaches curtail the rights to health, informed consent, privacy, freedom from non-consensual treatment, freedom from inhumane and degrading treatment, and freedom of movement of people lost to follow-up. Detention could also worsen social inequalities and lead to a paradoxical increase in TB incidence.

In the light of this information, the interventions which tackle the risk factors associated with LTFU are far superior to detention, which provides just a temporary solution to the problem, not a permanent one.

Another form of federal public health intervention is used in the USA to solve the problem of LTFU among the migrants [65]. These tools called the Do Not Board (DNB) and Border Lookout (BL) list are managed by the Department of Homeland Security (DHS) according to requests from the Centers for Disease Control and Prevention (CDC) Travel Restriction and Intervention expert workgroup. They are designed to detect land border travelers who were LTFU from TB treatment. State health departments and local health jurisdictions supply the list of patients and were reviewed under the following criteria:

(1) infectiousness or potential infectiousness with a communicable disease that would pose a public health threat if the individual travelled internationally;

(2) the person is unaware of his/her diagnosis, fails to adhere to public health recommendations, including treatment, or public health authorities are unable to locate the person; and

(3) the person poses a risk to travel internationally or on a commercial flight” [65].

Analysis revealed that most of the patients from this list were successfully treated but most of the migrants remain LTFU, suggesting that some improvement to the program is still needed to handle this problem.

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7. Conclusion

LTFU from treatment is a serious problem that cannot be ignored. Throughout this chapter, the consequences of LTFU, the magnitude of this problem in different countries, and the underlying factors have been discussed. Various researchers have designed potentially powerful interventions to tackle LTFU. But, we still need further evidence and actions to be able to successfully lower the number of patients that are LTFU. With these points in mind, it is suggested that an ambitious approach should be taken to reduce the number of LTFU patients up to 0%.

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Acknowledgments

I would like to thank Dr. Pa Pa Soe, associate professor, Department of Preventive and Social Medicine, University of Medicine 1, Yangon, for her invaluable advice on writing this book chapter. I am also truly grateful to Dr. Kyaw Khan Zaw, Technical Support Officer, Population Services International, Yangon, Myanmar for reviewing the chapter and giving helpful comments.

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Conflict of interest

None declared.

References

  1. 1. Zachariah R, Harries AD, Srinath S, Ram S, Viney K, Singogo E, et al. Language in tuberculosis services: Can we change to patient-centred terminology and stop the paradigm of blaming the patients? The International Journal of Tuberculosis and Lung Disease. 2012;16(6):714-717
  2. 2. World Health Organization. Definitions and Reporting Framework for Tuberculosis–2013 Revision. 2013
  3. 3. Baliashvili D, Magee MJ, Kempker RR, Kuchukhidze G, Aslanikashvili A, Blumberg HM. Contacts of retreatment tuberculosis cases with a prior poor treatment outcome are at increased risk of latent tuberculosis infection. International Journal of Infectious Diseases. 2016;43:49-50
  4. 4. Viana PVS, Redner P, Ramos JP. Factors associated with loss to follow-up and death in cases of drug-resistant tuberculosis (DR-TB) treated at a reference center in Rio de Janeiro. Cadernos de Saúde Pública. 2018;34(5):e00048217
  5. 5. Tupasi TE, Garfin AMCG, Kurbatova EV, Mangan JM, Orillaza-Chi R, Naval LC, et al. Factors associated with loss to follow-up during treatment for multidrug-resistant tuberculosis, the Philippines, 2012-2014. Emerging Infectious Diseases. 2016;22(3):491-502
  6. 6. Alene KA, Yi H, Viney K, McBryde ES, Yang K, Bai L, et al. Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China. BMC Infectious Diseases. 2017;17(1):573
  7. 7. Masini EO, Mansour O, Speer CE, Addona V, Hanson CL, Sitienei JK, et al. Using survival analysis to identify risk factors for treatment interruption among new and retreatment tuberculosis patients in Kenya. PLoS One. 2016;11(10):e0164172
  8. 8. Moyo S, Cox HS, Hughes J, Daniels J, Synman L, De Azevedo V, et al. Loss from treatment for drug resistant tuberculosis: Risk factors and patient outcomes in a community-based program in Khayelitsha, South Africa. PLoS One. 2015;10(3):e0118919. DOI: 10.1371/journal.pone.0118919
  9. 9. Loveday M, Ramjee A, Osburn G, Master I, Kabera G, Brust JCM, et al. Drug-resistant tuberculosis in patients with minimal symptoms: Favourable outcomes in the absence of treatment. The International Journal of Tuberculosis and Lung Disease. 2017;21(5):556-563
  10. 10. Trebucq A, Schwoebel V, Kashongwe Z, Bakayoko A, Kuaban C, Noeske J, et al. Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries. The International Journal of Tuberculosis and Lung Disease. 2018;22(1):17-25
  11. 11. Millett ERC, Noel D, Mangtani P, Abubakar I, Kruijshaar ME. Factors associated with being lost to follow-up before completing tuberculosis treatment: Analysis of surveillance data. Epidemiology and Infection. 2013;141(6):1223-1231
  12. 12. Randremanana RV, Richard V, Rakotomanana F, Sabatier P, Bicout DJ. Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar. BMC Infectious Diseases. 2010;10:21
  13. 13. Dahle UR. Extensively drug resistant tuberculosis: Beware patients lost to follow-up. BMJ. 2006;333:705
  14. 14. Dahle UR, Sandven P, Heldal E, Mannsaaker T, Caugant DA. Deciphering an outbreak of drug-resistant Mycobacterium tuberculosis. Journal of Clinical Microbiology. 2003;41(1):67-72
  15. 15. Mitruka K, Blake H, Ricks P, Miramontes R, Bamrah S, Chee C, et al. A tuberculosis outbreak fueled by cross-border travel and illicit substances: Nevada and Arizona. Public Health Reports. 2014;129(1):78-85
  16. 16. Schmid D, Fretz R, Kuo H-W, Rumetshofer R, Meusburger S, Magnet E, et al. An outbreak of multidrug-resistant tuberculosis among refugees in Austria, 2005-2006. The International Journal of Tuberculosis and Lung Disease. 2008;12(10):1190-1195
  17. 17. Thet Lwin ZM, Sahu SK, Owiti P, Chinnakali P, Majumdar SS. Public-private mix for tuberculosis care and control in Myanmar: A strategy to scale up? Public Health Action. 2017;7(1):15-20
  18. 18. Gadoev J, Asadov D, Tillashaykhov M, Tayler-Smith K, Isaakidis P, Dadu A, et al. Factors associated with unfavorable treatment outcomes in new and previously treated tb patients in Uzbekistan: A five year countrywide study. PLoS One. 2015;10(6):e0128907
  19. 19. Wikman-Jorgensen PE, Morales-Cartagena A, Llenas-Garcia J, Perez-Porcuna TM, Hobbins M, Ehmer J, et al. Implementation challenges of a TB programme in rural northern mozambique: Evaluation of 2012-2013 outcomes. Pathogens and Global Health. 2015;109(5):221-227
  20. 20. van Lettow M, Bedell R, Maosa S, Phiri K, Chan AK, Mwinjiwa E, et al. Outcomes and diagnostic processes in outpatients with presumptive tuberculosis in Zomba District, Malawi. PLoS One. 2015;10(11):e0141414
  21. 21. Wondale B, Medihn G, Teklu T, Mersha W, Tamirat M, Ameni G. A retrospective study on tuberculosis treatment outcomes at Jinka general hospital, southern Ethiopia. BMC Research Notes. 2017;10(1):680
  22. 22. Conaty SJ, Dart S, Hayward AC, Lipman MC. Reasons for low reported treatment success in notified tuberculosis patients from a London hospital according to new outcome reporting. Communicable Disease and Public Health. 2004;7(1):73-76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15137286
  23. 23. Cayla JA, Rodrigo T, Ruiz-Manzano J, Caminero JA, Vidal R, Garcia JM, et al. Tuberculosis treatment adherence and fatality in Spain. Respiratory Research. 2009;10:121
  24. 24. Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: Systematic review and meta-analysis. The Lancet Infectious Diseases. 2009;9(3):153-161. DOI: 10.1016/S1473-3099(09)70041-6
  25. 25. Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM. Treatment outcomes of multidrug-resistant tuberculosis: A systematic review and meta-analysis. PLoS One. 2009;4(9):e6914
  26. 26. Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bauer M, Bayona JN, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: An individual patient data meta-analysis of 9,153 patients. PLoS Medicine. 2012;9(8):e1001300
  27. 27. Anderson LF, Tamne S, Watson JP, Cohen T, Mitnick C, Brown T, et al. Treatment outcome of multi-drug resistant tuberculosis in the United Kingdom: Retrospective-prospective cohort study from 2004 to 2007. Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles = European Communicable Disease Bulletin. 2013;18(40):pii=20601
  28. 28. Jagielski T, Brzostek A, van Belkum A, Dziadek J, Augustynowicz-Kopec E, Zwolska Z. A close-up on the epidemiology and transmission of multidrug-resistant tuberculosis in Poland. European Journal of Clinical Microbiology & Infectious Diseases. 2015;34(1):41-53
  29. 29. Atif M, Bashir A, Ahmad N, Fatima RK, Saba S, Scahill S. Predictors of unsuccessful interim treatment outcomes of multidrug resistant tuberculosis patients. BMC Infectious Diseases. 2017;17(1):655
  30. 30. Jensenius M, Winje BA, Blomberg B, Mengshoel AT, von der Lippe B, Hannula R, et al. Multidrug-resistant tuberculosis in Norway: A nationwide study, 1995-2014. The International Journal of Tuberculosis and Lung Disease. 2016;20(6):786-792
  31. 31. Cegielski JP, Kurbatova E, van der Walt M, Brand J, Ershova J, Tupasi T, et al. Multidrug-resistant tuberculosis treatment outcomes in relation to treatment and initial versus acquired second-line drug resistance. Clinical Infectious Diseases. 2016;62(4):418-430
  32. 32. Gadallah MA, Mokhtar A, Rady M, El-Moghazy E, Fawzy M, Kandil SK. Prognostic factors of treatment among patients with multidrug-resistant tuberculosis in Egypt. Journal of the Formosan Medical Association. 2016;115(11):997-1003
  33. 33. Kasapo CC, Chimzizi R, Simwanza SC, Mzyece J, Chizema E, Mariandyshev A, et al. What happened to patients with RMP-resistant/MDR-TB in Zambia reported as lost to follow-up from 2011 to 2014? The International Journal of Tuberculosis and Lung Disease. 2017;21(8):887-893
  34. 34. Yu M-C, Chiang C-Y, Lee J-J, Chien S-T, Lin C-J, Lee S-W, et al. Treatment outcomes of multidrug-resistant tuberculosis in Taiwan: Tackling loss to follow-up. Clinical Infectious Diseases. 2018;67(2):202-221
  35. 35. Huerga H, Bastard M, Kamene M, Wanjala S, Arnold A, Oucho N, et al. Outcomes from the first multidrug-resistant tuberculosis programme in Kenya. The International Journal of Tuberculosis and Lung Disease. 2017;21(3):314-319
  36. 36. Alene KA, Viney K, McBryde ES, Tsegaye AT, Clements ACA. Treatment outcomes in patients with multidrug-resistant tuberculosis in north-west Ethiopia. Tropical Medicine & International Health. 2017;22(3):351-362
  37. 37. Cavanaugh JS, Kazennyy BY, Nguyen ML, Kiryanova EV, Vitek E, Khorosheva TM, et al. Outcomes and follow-up of patients treated for multidrug-resistant tuberculosis in Orel, Russia, 2002-2005. The International Journal of Tuberculosis and Lung Disease. 2012;16(8):1069-1074
  38. 38. Shringarpure KS, Isaakidis P, Sagili KD, Baxi RK. Loss-to-follow-up on multidrug resistant tuberculosis treatment in Gujarat, India: The when and who of it. PLoS One. 2015;10(7):e0132543
  39. 39. Thu MK, Kumar AMV, Soe KT, Saw S, Thein S, Mynit Z, et al. High treatment success rate among multidrug-resistant tuberculosis patients in Myanmar, 2012-2014: A retrospective cohort study. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2017;111(9):410-417
  40. 40. Khaliaukin A, Kumar AMV, Skrahina A, Hurevich H, Rusovich V, Gadoev J, et al. Poor treatment outcomes among multidrug-resistant tuberculosis patients in Gomel Region, Republic of Belarus. Public Health Action. 2014;4(Suppl 2):S24-S28
  41. 41. Kuchukhidze G, Kumar AMV, de Colombani P, Khogali M, Nanava U, Blumberg HM, et al. Risk factors associated with loss to follow-up among multidrug-resistant tuberculosis patients in Georgia. Public Health Action. 2014;4(Suppl 2):S41-S46
  42. 42. Zhang L, Meng Q, Chen S, Zhang M, Chen B, Wu B, et al. Treatment outcomes of multidrug-resistant tuberculosis patients in Zhejiang, China, 2009-2013. Clinical Microbiology and Infection. 2018;24(4):381-388
  43. 43. Parmar MM, Sachdeva KS, Dewan PK, Rade K, Nair SA, Pant R, et al. Unacceptable treatment outcomes and associated factors among India’s initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007-2011): Evidence leading to policy enhancement. PLoS One. 2018;13(4):e0193903
  44. 44. Lanoix J-P, Douadi Y, Borel A, Andrejak C, El Samad Y, Ducroix J-P, et al. Lymph node tuberculosis treatment: From recommendations to practice. Médecine et Maladies Infectieuses. 2011;41(2):87-91
  45. 45. Mouba JF, Miloundja J, Mimbila-Mayi M, Ndjenkam FT, N’zouba L. Cervical lymph node tuberculosis in Libreville: Epidemiology, diagnosis, and therapy. Santé. 2011;21(3):165-168
  46. 46. Garg RK, Sharma R, Kar AM, Kushwaha RAS, Singh MK, Shukla R, et al. Neurological complications of miliary tuberculosis. Clinical Neurology and Neurosurgery. 2010;112(3):188-192
  47. 47. AlSemari A, Baz S, Alrabiah F, Al-Khairallah T, Qadi N, Kareem A, et al. Natural course of epilepsy concomitant with CNS tuberculomas. Epilepsy Research. 2012;99(1-2):107-111
  48. 48. Peluso MJ, Hung A, Lukasiewicz A, Chang H, Ramallo J, Bartlett M, et al. Successful management of latent tuberculosis infection in an underserved community by a student-run free clinic. Journal of Health Care for the Poor and Underserved. 2014 May;25(2):837-862
  49. 49. Kwara A, Herold JS, Machan JT, Carter EJ. Factors associated with failure to complete isoniazid treatment for latent tuberculosis infection in Rhode Island. Chest. 2008;133(4):862-868
  50. 50. Clerk N, Sisson K, Antunes G. Latent tuberculosis: Concordance and duration of treatment regimens. The British Journal of Nursing. 2011;20(13):824-827
  51. 51. Langenskiold E, Herrmann FR, Luong BL, Rochat T, Janssens J-P. Contact tracing for tuberculosis and treatment for latent infection in a low incidence country. Swiss Medical Weekly. 2008;138(5-6):78-84
  52. 52. Flick RJ, Kim MH, Simon K, Munthali A, Hosseinipour MC, Rosenberg NE, et al. Burden of disease and risk factors for death among children treated for tuberculosis in Malawi. The International Journal of Tuberculosis and Lung Disease. 2016;20(8):1046-1054
  53. 53. Engohan Alloghe E, Toung Mve M, Ramarojoana S, Iba J, Nkoghe D. Epidemiology of childhood tuberculosis in Libreville, Gabon from 1997 to 2001. La Medicina Tropical. 2006;66(5):469-471
  54. 54. Segbedji KAR, Djadou KE, Tchagbele O-B, Kpegouni M, Bessi Kama LK, Azoumah KD, et al. Tuberculosis in children in Togo: Epidemiology, diagnosis, treatment, and outcome. Medecine et Sante Tropicales. 2016;26(3):318-322
  55. 55. Iroh Tam PY, Menon A, Butler K. A review of tuberculosis-related referrals among children in Ireland. Irish Journal of Medical Science. 2010;179(2):251-254
  56. 56. Panigatti P, Ratageri VH, Shivanand I, Madhu PK, Shepur TA. Profile and outcome of childhood tuberculosis treated with DOTS—An observational study. Indian Journal of Pediatrics. 2014;81(1):9-14
  57. 57. Pekcan S, Tana Aslan A, Kiper N, Uysal G, Gurkan F, Patiroglu T, et al. Multicentric analysis of childhood tuberculosis in Turkey. The Turkish Journal of Pediatrics. 2013;55(2):121-129
  58. 58. Seddon JA, Hesseling AC, Godfrey-Faussett P, Schaaf HS. High treatment success in children treated for multidrug-resistant tuberculosis: An observational cohort study. Thorax. 2014;69(5):458-464
  59. 59. Shah MA, Shah I. Increasing prevalence of pediatric drug-resistant tuberculosis in Mumbai, India and its outcome. The Pediatric Infectious Disease Journal. 2018;37(12):1261-1263
  60. 60. Chiang SS, Starke JR, Miller AC, Cruz AT, Del Castillo H, Valdivia WJ, et al. Baseline predictors of treatment outcomes in children with multidrug-resistant tuberculosis: A retrospective cohort study. Clinical Infectious Diseases. 2016;63(8):1063-1071
  61. 61. Horo K, Toure K, Brou-Gode V-C, Ahui BJ-M, Kouassi B-A, Gnaze A-Z, et al. Tuberculosis in the elderly: Epidemiology and outcomes of ambulatory followed-up in Abidjan. Revue d’Épidémiologie et de Santé Publique. 2012;60(6):484-488
  62. 62. Laraqui CH, Ottmani S, Hammou MA, Bencheikh N, Mahjour J. Study of tuberculosis in health care workers in the public sector of Morocco. The International Journal of Tuberculosis and Lung Disease. 2001;5(10):939-945
  63. 63. Adane K, Spigt M, Dinant G-J. Tuberculosis treatment outcome and predictors in northern Ethiopian prisons: A five-year retrospective analysis. BMC Pulmonary Medicine. 2018;18(1):37
  64. 64. Schwitters A, Kaggwa M, Omiel P, Nagadya G, Kisa N, Dalal S. Tuberculosis incidence and treatment completion among Ugandan prison inmates. The International Journal of Tuberculosis and Lung Disease. 2014;18(7):781-786
  65. 65. DeSisto C, Broussard K, Escobedo M, Borntrager D, Alvarado-Ramy F, Waterman S. Border lookout: Enhancing tuberculosis control on the United States-Mexico border. The American Journal of Tropical Medicine and Hygiene. 2015;93(4):747-751
  66. 66. Gray NJ, Hansen-Knarhoi M, Krause VL. Tuberculosis in illegal foreign fishermen: Whose public health are we protecting? The Medical Journal of Australia. 2008;188(3):144-147
  67. 67. Ward HA, Marciniuk DD, Hoeppner VH, Jones W. Treatment outcome of multidrug-resistant tuberculosis among Vietnamese immigrants. The International Journal of Tuberculosis and Lung Disease. 2005;9(2):164-169
  68. 68. Patra S, Lukhmana S, Tayler Smith K, Kannan AT, Satyanarayana S, Enarson DA, et al. Profile and treatment outcomes of elderly patients with tuberculosis in Delhi, India: Implications for their management. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2013;107(12):763-768
  69. 69. Velayutham BRV, Nair D, Chandrasekaran V, Raman B, Sekar G, Watson B, et al. Profile and response to anti-tuberculosis treatment among elderly tuberculosis patients treated under the TB Control programme in South India. PLoS One. 2014;9(3):e88045
  70. 70. Lin Y, Enarson DA, Du J, Dlodlo RA, Chiang C-Y, Rusen ID. Risk factors for unfavourable treatment outcome among new smear-positive pulmonary tuberculosis cases in China. Public Health Action. 2017;7(4):299-303
  71. 71. Enane LA, Lowenthal ED, Arscott-Mills T, Matlhare M, Smallcomb LS, Kgwaadira B, et al. Loss to follow-up among adolescents with tuberculosis in Gaborone, Botswana. The International Journal of Tuberculosis and Lung Disease. 2016;20(10):1320-1325
  72. 72. Dangisso MH, Datiko DG, Lindtjorn B. Trends of tuberculosis case notification and treatment outcomes in the Sidama Zone, southern Ethiopia: Ten-year retrospective trend analysis in urban-rural settings. PLoS One. 2014;9(12):e114225
  73. 73. Javaid A, Shaheen Z, Shafqat M, Khan AH, Ahmad N. Risk factors for high death and loss-to-follow-up rates among patients with multidrug-resistant tuberculosis at a programmatic management unit. American Journal of Infection Control. 2017;45(2):190-193
  74. 74. Bemba ELP, Bopaka RG, Ossibi-Ibara R, Toungou SN, Ossale-Abacka BK, Okemba-Okombi FH, et al. Predictive factors of lost to follow-up status during tuberculosis treatment in Brazzaville. Revue de Pneumologie Clinique. 2017;73(2):81-89
  75. 75. Mainbourg EMT, Belchior ADS, Goncalves MJF. Loss to follow-up in tuberculosis treatment and its relationship with patients’ knowledge of the disease and other associated factors. Rev Salud Pública. 2017;18(5):714. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28453113
  76. 76. Li T, Zhang H, Wang LX, Pang Y, DU X. Description and factors affecting the referral of presumptive tuberculosis patients in China. Biomedical and Environmental Sciences. 2017;30(6):444-449
  77. 77. Deshmukh RD, Dhande DJ, Sachdeva KS, Sreenivas A, Kumar AMV, Satyanarayana S, et al. Patient and provider reported reasons for lost to follow up in MDRTB treatment: A qualitative study from a drug resistant TB centre in India. PLoS One. 2015;10(8):e0135802
  78. 78. Park C-K, Shin H-J, Kim Y-I, Lim S-C, Yoon J-S, Kim Y-S, et al. Predictors of default from treatment for tuberculosis: A single center case-control study in Korea. Journal of Korean Medical Science. 2016;31(2):254-260
  79. 79. Brainard D, Hyslop NE, Mera R, Churchill J. Long-term outcome of inpatients with tuberculosis assigned to outpatient therapy at a local clinic in New Orleans. Journal of Investigative Medicine. 1997;45(6):381-387
  80. 80. Conwell DS, Mosher A, Khan A, Tapy J, Sandman L, Vernon A, et al. Factors associated with loss to follow-up in a large tuberculosis treatment trial (TBTC Study 22). Contemporary Clinical Trials. 2007;28(3):288-294
  81. 81. Story A, Murad S, Roberts W, Verheyen M, Hayward AC. Tuberculosis in London: The importance of homelessness, problem drug use and prison. Thorax. 2007;62(8):667-671
  82. 82. Ogbudebe CL, Izuogu S, Abu CE. Magnitude and treatment outcomes of pulmonary tuberculosis patients in a poor urban slum of Abia State, Nigeria. International Journal of Mycobacteriology. 2016;5(2):205-210
  83. 83. Ade S, Harries AD, Trebucq A, Ade G, Agodokpessi G, Adjonou C, et al. National profile and treatment outcomes of patients with extrapulmonary tuberculosis in Benin. PLoS One. 2014;9(4):e95603
  84. 84. Mi F, Tan S, Liang L, Harries AD, Hinderaker SG, Lin Y, et al. Diabetes mellitus and tuberculosis: Pattern of tuberculosis, two-month smear conversion and treatment outcomes in Guangzhou, China. Tropical Medicine & International Health. 2013;18(11):1379-1385
  85. 85. Asres A, Jerene D, Deressa W. Delays to treatment initiation is associated with tuberculosis treatment outcomes among patients on directly observed treatment short course in Southwest Ethiopia: A follow-up study. BMC Pulmonary Medicine. 2018;18(1):64
  86. 86. Nwe TT, Saw S, Le Win L, Mon MM, van Griensven J, Zhou S, et al. Engagement of public and private medical facilities in tuberculosis care in Myanmar: Contributions and trends over an eight-year period. Infectious Diseases of Poverty. 2017;6(1):123
  87. 87. Adejumo OA, Daniel OJ, Otesanya AF, Salisu-Olatunj SO, Abdur-Razzaq HA. Evaluation of outcomes of tuberculosis management in private for profit and private-not-for profit directly observed treatment short course facilities in Lagos State, Nigeria. Nigerian Medical Journal. 2017;58(1):44-49
  88. 88. Shringarpure KS, Isaakidis P, Sagili KD, Baxi RK. Loss-to-follow-up on multidrug resistant tuberculosis treatment in Gujarat, India: The when and who of it. PLoS One. 2015;10(7):1-10
  89. 89. Anyama N, Bracebridge S, Black C, Niggebrugge A, Griffin SJ. What happens to people diagnosed with tuberculosis? A population-based cohort. Epidemiology and Infection. 2007;135(7):1069-1076
  90. 90. Min GH, Kim Y, Lee JS, Oh JY, Hur GY, Lee YS, et al. Social and clinical characteristics of immigrants with tuberculosis in South Korea. Yonsei Medical Journal. 2017;58(3):592-597
  91. 91. Rodrigo T, Cayla JA, Casals M, Garcia-Garcia JM, Caminero JA, Ruiz-Manzano J, et al. A predictive scoring instrument for tuberculosis lost to follow-up outcome. Respiratory Research. 2012;13:75
  92. 92. Asuquo Otu A. Is the directly observed therapy short course (DOTS) an effective strategy for tuberculosis control in a developing country? Asian Pacific Journal of Tropical Medicine. 2013;3(3):227-231
  93. 93. Karumbi J, Garner P. Directly observed therapy for treating tuberculosis. Cochrane Database of Systematic Reviews. 2015;5:CD003343
  94. 94. World Health Organization. mHealth: New Horizons for Health Through Mobile Technologies. World Health Organization; 2011
  95. 95. Hermans SM, Elbireer S, Tibakabikoba H, Hoefman BJ, Manabe YC. Text messaging to decrease tuberculosis treatment attrition in TB-HIV coinfection in Uganda. Patient Preference and Adherence. 2017;11:1479-1487
  96. 96. Operation ASHA. eCOMPLIANCE [Internet]. 2018. Available from: https://www.opasha.org/blog/2016/09/20/ecompliance-biometric-tracking-system/ [Accessed: 01 September 2018]
  97. 97. Snidal SJ, Barnard G, Atuhairwe E, Ben AY. Use of eCompliance, an innovative biometric system for monitoring of tuberculosis treatment in rural Uganda. The American Journal of Tropical Medicine and Hygiene. 2015;92(6):1271-1279
  98. 98. Yassin MA, Datiko DG, Tulloch O, Markos P, Aschalew M, Shargie EB, et al. Innovative community-based approaches doubled tuberculosis case notification and improve treatment outcome in southern Ethiopia. PLoS One. 2013;8(5):1-8
  99. 99. Datiko DG, Yassin MA, Theobald SJ, Blok L, Suvanand S, Creswell J, et al. Health extension workers improve tuberculosis case finding and treatment outcome in Ethiopia: A large-scale implementation study. BMJ Global Health. 2017;2(4):e000390
  100. 100. Balakrishnan S, Manikantan J, Sreenivas A, Jayasankar S, Sunilkumar M, Rakesh PS, et al. Social inclusion: An effort to end loss-to-treatment follow-up in tuberculosis. The Indian Journal of Tuberculosis. 2015;62(4):230-234
  101. 101. Getahun B, Nkosi ZZ. Is directly observed tuberculosis treatment strategy patient-centered? a mixed method study in Addis Ababa, Ethiopia. PLoS One. 2017;12(8):e0181205
  102. 102. Burman WJ, Cohn DL, Rietmeijer CA, Judson FN, Sbarbaro JA, Reves RR. Short-term incarceration for the management of noncompliance with tuberculosis treatment. Chest. 1997;112(1):57-62
  103. 103. Mburu G, Restoy E, Kibuchi E, Holland P, Harries AD. Detention of people lost to follow-up on tb treatment in Kenya: The need for human rights-based alternatives. Health and Human Rights. 2016;18(1):43-54

Written By

Kyaw San Lin

Submitted: May 25th, 2018 Reviewed: October 8th, 2018 Published: September 16th, 2019