Outcome Impacts Due to Pathogen-Specific Antimicrobial Resistance: A Narrative Review of Published Literature
Identifieur interne : 000A06 ( Pmc/Curation ); précédent : 000A05; suivant : 000A07Outcome Impacts Due to Pathogen-Specific Antimicrobial Resistance: A Narrative Review of Published Literature
Auteurs : Tingting Jiang [République populaire de Chine] ; Xiang-Sheng Chen [République populaire de Chine]Source :
- International Journal of Environmental Research and Public Health [ 1661-7827 ] ; 2020.
Abstract
Antimicrobial resistance (AMR) has become a global threat to not only public health impacts but also clinical and economic outcomes. During the past decades, there have been many studies focusing on surveillance, mechanisms, and diagnostics of AMR in infectious diseases but the impacts on public health, clinical and economic outcomes due to emergence of these AMRs are rarely studied and reported. This review was aimed to summarize the findings from published studies to report the outcome impacts due to AMR of malaria, tuberculosis and HIV and briefly discuss the implications for application to other infectious diseases. PubMed/Medline and Google Scholar databases were used for search of empirical and peer-reviewed papers reporting public health, clinical and economic outcomes due to AMR of malaria, tuberculosis and HIV. Papers published through 1 December 2019 were included in this review. A total of 76 studies were included for this review, including 16, 49 and 11 on public health, clinical and economic outcomes, respectively. The synthesized data indicated that the emergence and spread of AMR of malaria, tuberculosis and HIV have resulted in adverse public health, clinical and economic outcomes. AMR of malaria, tuberculosis and HIV results in significant adverse impacts on public health, clinical and economic outcomes. Evidence from this review suggests the needs to consider the similar studies for other infectious diseases.
Url:
DOI: 10.3390/ijerph17041395
PubMed: 32098182
PubMed Central: 7068360
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<front><div type="abstract" xml:lang="en"><p>Antimicrobial resistance (AMR) has become a global threat to not only public health impacts but also clinical and economic outcomes. During the past decades, there have been many studies focusing on surveillance, mechanisms, and diagnostics of AMR in infectious diseases but the impacts on public health, clinical and economic outcomes due to emergence of these AMRs are rarely studied and reported. This review was aimed to summarize the findings from published studies to report the outcome impacts due to AMR of malaria, tuberculosis and HIV and briefly discuss the implications for application to other infectious diseases. PubMed/Medline and Google Scholar databases were used for search of empirical and peer-reviewed papers reporting public health, clinical and economic outcomes due to AMR of malaria, tuberculosis and HIV. Papers published through 1 December 2019 were included in this review. A total of 76 studies were included for this review, including 16, 49 and 11 on public health, clinical and economic outcomes, respectively. The synthesized data indicated that the emergence and spread of AMR of malaria, tuberculosis and HIV have resulted in adverse public health, clinical and economic outcomes. AMR of malaria, tuberculosis and HIV results in significant adverse impacts on public health, clinical and economic outcomes. Evidence from this review suggests the needs to consider the similar studies for other infectious diseases.</p>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Environ Res Public Health</journal-id>
<journal-id journal-id-type="iso-abbrev">Int J Environ Res Public Health</journal-id>
<journal-id journal-id-type="publisher-id">ijerph</journal-id>
<journal-title-group><journal-title>International Journal of Environmental Research and Public Health</journal-title>
</journal-title-group>
<issn pub-type="ppub">1661-7827</issn>
<issn pub-type="epub">1660-4601</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">32098182</article-id>
<article-id pub-id-type="pmc">7068360</article-id>
<article-id pub-id-type="doi">10.3390/ijerph17041395</article-id>
<article-id pub-id-type="publisher-id">ijerph-17-01395</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Outcome Impacts Due to Pathogen-Specific Antimicrobial Resistance: A Narrative Review of Published Literature</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Jiang</surname>
<given-names>Tingting</given-names>
</name>
<xref ref-type="aff" rid="af1-ijerph-17-01395">1</xref>
<xref ref-type="aff" rid="af2-ijerph-17-01395">2</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-3927-2065</contrib-id>
<name><surname>Chen</surname>
<given-names>Xiang-Sheng</given-names>
</name>
<xref ref-type="aff" rid="af1-ijerph-17-01395">1</xref>
<xref ref-type="aff" rid="af2-ijerph-17-01395">2</xref>
<xref rid="c1-ijerph-17-01395" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-ijerph-17-01395"><label>1</label>
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China;<email>jiangtt@ncstdlc.org</email>
</aff>
<aff id="af2-ijerph-17-01395"><label>2</label>
National Center for STD Control, Chinese Center for Disease Control and Prevention, Nanjing 210042, China</aff>
<author-notes><corresp id="c1-ijerph-17-01395"><label>*</label>
Correspondence: <email>chenxs@ncstdlc.org</email>
; Tel.: +86-25-8547-8901</corresp>
</author-notes>
<pub-date pub-type="epub"><day>21</day>
<month>2</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="ppub"><month>2</month>
<year>2020</year>
</pub-date>
<volume>17</volume>
<issue>4</issue>
<elocation-id>1395</elocation-id>
<history><date date-type="received"><day>15</day>
<month>1</month>
<year>2020</year>
</date>
<date date-type="accepted"><day>19</day>
<month>2</month>
<year>2020</year>
</date>
</history>
<permissions><copyright-statement>© 2020 by the authors.</copyright-statement>
<copyright-year>2020</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>Antimicrobial resistance (AMR) has become a global threat to not only public health impacts but also clinical and economic outcomes. During the past decades, there have been many studies focusing on surveillance, mechanisms, and diagnostics of AMR in infectious diseases but the impacts on public health, clinical and economic outcomes due to emergence of these AMRs are rarely studied and reported. This review was aimed to summarize the findings from published studies to report the outcome impacts due to AMR of malaria, tuberculosis and HIV and briefly discuss the implications for application to other infectious diseases. PubMed/Medline and Google Scholar databases were used for search of empirical and peer-reviewed papers reporting public health, clinical and economic outcomes due to AMR of malaria, tuberculosis and HIV. Papers published through 1 December 2019 were included in this review. A total of 76 studies were included for this review, including 16, 49 and 11 on public health, clinical and economic outcomes, respectively. The synthesized data indicated that the emergence and spread of AMR of malaria, tuberculosis and HIV have resulted in adverse public health, clinical and economic outcomes. AMR of malaria, tuberculosis and HIV results in significant adverse impacts on public health, clinical and economic outcomes. Evidence from this review suggests the needs to consider the similar studies for other infectious diseases.</p>
</abstract>
<kwd-group><kwd>antimicrobial resistance</kwd>
<kwd>outcome impacts</kwd>
<kwd>malaria</kwd>
<kwd>tuberculosis</kwd>
<kwd>HIV</kwd>
<kwd>infectious diseases</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="ijerph-17-01395-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>PRISMA flow diagram.</p>
</caption>
<graphic xlink:href="ijerph-17-01395-g001"></graphic>
</fig>
<fig id="ijerph-17-01395-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Articles finally included into narrative review were categorized according to disease (malaria, tuberculosis and HIV) field of interest (public health, clinical and economic outcomes).</p>
</caption>
<graphic xlink:href="ijerph-17-01395-g002"></graphic>
</fig>
<table-wrap id="ijerph-17-01395-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">ijerph-17-01395-t001_Table 1</object-id>
<label>Table 1</label>
<caption><p>Characteristics of included studies on public health outcomes due to AMR.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author by Disease</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Year</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Site</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Sample Size</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Design/Method</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcome</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Quality Assessment</th>
</tr>
</thead>
<tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Malaria</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Warsame et al. [<xref rid="B14-ijerph-17-01395" ref-type="bibr">14</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1982–1988</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Somalia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">109</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The emergence of chloroquine resistance, accelerated by high drug pressure, low herd immunity and favourable meteorological conditions were identified as major causes of the epidemic of falciparum malaria in Balcad, Somalia.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sharma et al. [<xref rid="B15-ijerph-17-01395" ref-type="bibr">15</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1994</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">India</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">32</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In 1994, there was a falciparum malaria epidemic in Rajasthan, India, with many deaths, and most of the parasite isolates (95%) were resistant to chloroquine.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Knight et al. [<xref rid="B16-ijerph-17-01395" ref-type="bibr">16</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1982–1988, 1991–2001</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">South Africa</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">600000</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ecological study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The relative risk for malaria infection after the level of drug resistance reached 10% was 4.5 (95% CI: 4.0–5.2) in the chloroquine period and 5.9 (95% CI: 5.7–6.1) in the sulfadoxine-pyrimethamine period.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MODERATE</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Slater et al. [<xref rid="B17-ijerph-17-01395" ref-type="bibr">17</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2016–2020</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Africa</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">An individual-based malaria transmission model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Artemisinin and partner drug resistance at levels similar to those observed in Oddar Meanchey province in Cambodia could result in an additional 78 million cases over a 5 year period, a 7% increase in cases compared to a scenario with no resistance.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tuberculosis</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Reves et al. [<xref rid="B18-ijerph-17-01395" ref-type="bibr">18</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1976</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">15</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective investigation</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">An outbreak of tuberculosis in 1976 was caused by mycobacteria resistant to isoniazid (INH), streptomycin (SM), and para-aminosalicylic acid (PAS).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ussery et al. [<xref rid="B19-ijerph-17-01395" ref-type="bibr">19</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1995</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A trend between TST conversion and participation in autopsies on persons with MDR-TB was observed.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Coronado et al. [<xref rid="B20-ijerph-17-01395" ref-type="bibr">20</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1990–1991</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">From January 1990 to December 1991, 16 patients with multidrug-resistant tuberculosis (MDR-TB) were caused by nosocomial transmission of MDR-TB resistant to isoniazid, rifampin, and streptomycin.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Friedman et al. [<xref rid="B21-ijerph-17-01395" ref-type="bibr">21</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1995</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">167</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Forty-three (34%) of 127 drug-susceptible isolates and 19 (79%) of 24 multidrug-resistant isolates had RFLP patterns representing possible recent exogenous infection.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">US CDC. [<xref rid="B22-ijerph-17-01395" ref-type="bibr">22</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1990–1991</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">During 1990 and 1991, outbreaks of multidrug-resistant tuberculosis (MDR-TB) in four hospitals (one in Miami and three in New York City) were due to nosocomial transmission among HIV-infected persons.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nivin et al. [<xref rid="B23-ijerph-17-01395" ref-type="bibr">23</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1998</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nosocomial transmission appeared to account for an increase in cases of multidrug-resistant tuberculosis (MDRTB) at a large urban facility where a prior nosocomial outbreak of MDRTB had occurred.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Powell et al. [<xref rid="B24-ijerph-17-01395" ref-type="bibr">24</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2008–2015</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">110</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective investigation</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Of 110 outbreak cases in Georgia, 86 (78%) were culture confirmed and isoniazid resistant.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mehra et al. [<xref rid="B25-ijerph-17-01395" ref-type="bibr">25</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2010–2050</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">China</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dynamic state transition model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In China, by 2050, incidence, prevalence and mortality of MDR-TB will increase by respectively 60%, 48% and 35%, which attributed to inappropriate treatment, leading to high transmission of infection and increased LTBI prevalence.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sharma et al. [<xref rid="B26-ijerph-17-01395" ref-type="bibr">26</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2000–2040</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">India, Philippines, Russia and South Africa</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A compartmental model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12.4% (95% prediction interval 9.4–16.2) in India, 8·9% (4.5–11.7) in the Philippines, 32.5% (27.0–35.8) in Russia, and 5·7% (3.0–7.6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5.1–12.9) in India, 9·0% (4.0–14.7) in the Philippines, 9·0% (4.8–14.2) in Russia, and 8·5% (2.5–14.7) in South Africa in 2040.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HIV</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Blower et al. [<xref rid="B27-ijerph-17-01395" ref-type="bibr">27</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1996–2005</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A mathematical model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The epidemic of resistance is being generated mainly by the conversion of drug-sensitive cases to drug-resistant cases, and not by the transmission of resistant strains.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Smith et al. [<xref rid="B28-ijerph-17-01395" ref-type="bibr">28</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2008–2013</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A biologically complex multistrain network model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">60% of the currently circulating ARV-resistant strains in San Francisco are capable of causing self-sustaining epidemics, because each individual infected with one of these strains can cause, on average, more than one new resistant infection.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Phillips et al. [<xref rid="B29-ijerph-17-01395" ref-type="bibr">29</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2016–2030</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sub-Saharan Africa</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HIV Synthesis Model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In a situation in which current levels of pretreatment HIVDR are over 10% (mean, 15%), 16% of AIDS deaths (890 000 deaths), 9% of new infections (450 000), and 8% ($6.5 billion) of ART program costs in SSA in 2016–2030 will be attributable to HIVDR.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>NR, not reported.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="ijerph-17-01395-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">ijerph-17-01395-t002_Table 2</object-id>
<label>Table 2</label>
<caption><p>Characteristics of included studies on clinical outcomes due to AMR.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author by Disease</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Year</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Site</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Sample Size</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Design/Method</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcome</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Quality Assessment</th>
</tr>
</thead>
<tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Malaria</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nsanzabana et al. [<xref rid="B30-ijerph-17-01395" ref-type="bibr">30</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1991–2002</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Papua New Guinea</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6678</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Treatment failure rates multiplied by 3.5 between 1996 and 2000 but then decreased dramatically after treatment policy change.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Khoromana et al. [<xref rid="B31-ijerph-17-01395" ref-type="bibr">31</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1978–1983</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Malawi</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">224</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Parasitological failure ranged from 41–65% following administration of chloroquine 25 mg (base)/kg.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MODERATE</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Greenberg et al. [<xref rid="B32-ijerph-17-01395" ref-type="bibr">32</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1982–1986</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zaire</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6208</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The proportional malaria admission rate increased from 29.5% in 1983 to 56.4% in 1986, and the proportional malaria mortality rate, from 4.8% in 1982 to 15.3% in 1986, which were temporally related to the emergence of chloroquine-resistant Plasmodium falciparum malaria in Kinshasa.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Carme et al. [<xref rid="B33-ijerph-17-01395" ref-type="bibr">33</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1983–1989</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Congo</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A retrospective and prospective hospital-based study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The results show a marked increase in hospitalizations for malaria, noticeable since 1985, and which now account for about 50% of the overall non-surgical hospitalizations.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Asindi et al. [<xref rid="B34-ijerph-17-01395" ref-type="bibr">34</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1986–1988</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nigeria</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">134</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Malaria was the dominant cause (73%) of febrile convulsion (FC); 81% of these cases did not respond to chloroquine.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zucker et al. [<xref rid="B35-ijerph-17-01395" ref-type="bibr">35</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1991</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Kenya</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1223</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Treatment for malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens (pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for five days).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Shanks et al. [<xref rid="B36-ijerph-17-01395" ref-type="bibr">36</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1980–1997</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Kenya</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10169</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The dramatic increases in the numbers of malaria admissions (6.5 to 32.5% of all admissions), case fatality (1.3 to 6%) and patients originating from low-risk, highland areas (34 to 59%) were probably due to chloroquine resistance during the late 1980s in the subregion.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zucker et al. [<xref rid="B37-ijerph-17-01395" ref-type="bibr">37</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1991–1994</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">western Kenya</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1223</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The trend in case-fatality rates for malaria decreased as an increasing proportion of children received an effective treatment regimen; adjusted malaria case-fatality rates were 5.1%, 3.6%, and 3.3% in 1992, 1993, and 1994, respectively, when 85% of children in 1992 and 97% of children in 1993–1994 received effective therapy.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Brewster et al. [<xref rid="B38-ijerph-17-01395" ref-type="bibr">38</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1988–1990</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Gambia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9584</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">With the emergence of chloroquine-resistant malaria over the 3 years, there was a 27% annual increase in severe anaemia owing to malaria.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Poespoprodjo et al. [<xref rid="B39-ijerph-17-01395" ref-type="bibr">39</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2004–2010</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Indonesia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7744</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In those with history of malaria during pregnancy, the increasing use of DHP was associated with a 54% fall in the proportion of maternal malaria at delivery and a 98% decrease in congenital malaria (from 7.1% prior to 0.1% after policy change).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Amaratunga et al. [<xref rid="B8-ijerph-17-01395" ref-type="bibr">8</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2012–2013</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cambodia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">241</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In Pursat, where artemisinin resistance is entrenched, 37 (46%) of 81 patients had parasite recrudescence. In Preah Vihear, where artemisinin resistance is emerging, ten (16%) of 63 patients had recrudescence and in Ratanakiri, where artemisinin resistance is rare, one (2%) of 60 patients did.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Leang et al. [<xref rid="B40-ijerph-17-01395" ref-type="bibr">40</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2011–2013</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cambodia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">425</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A prospective multicenter open-label study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The most significant risk factor associated with DHA-PP treatment failure was infection by parasites carrying the K13 mutant allele (odds ratio [OR], 17.5; 95% confidence interval [CI], 1 to 308; <italic>p</italic>
= 0.04).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Leang et al. [<xref rid="B41-ijerph-17-01395" ref-type="bibr">41</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2008–2011</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cambodia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">438</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In 2010, the PCR-corrected treatment failure rates for DP on day 42 were 25% (95% confidence interval [CI] = 10 to 51%) in Pailin and 10.7% (95% CI = 4 to 23%) in Pursat, while the therapeutic efficacy of DP remained high (100%) in Ratanakiri and Preah Vihear provinces, located in northern and eastern Cambodia.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Winter et al. [<xref rid="B42-ijerph-17-01395" ref-type="bibr">42</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In Silico Model for Antimalarial Drug Treatment and Failure</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The development of artemisinin tolerance and resistance will, unless checked, have an immediate, large impact on the protection afforded to its partner drug and on the likely clinical efficacy of artemisinin combination therapies.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tuberculosis</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Espinal et al. [<xref rid="B43-ijerph-17-01395" ref-type="bibr">43</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1994–1996</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dominican Republic, Hong Kong Special Administrative Region, Italy, Ivanovo Oblast, the Republic of Korea, and Peru</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6402</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Treatment failure (relative risk [RR], 15.4; 95% confidence interval [CI], 10.6–22.4; <italic>p</italic>
< 0.001) and mortality (RR, 3.73; 95% CI, 2.13–6.53; <italic>p</italic>
< 0.001) were higher among new multidrug-resistant TB cases than among new susceptible cases.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Singla et al. [<xref rid="B44-ijerph-17-01395" ref-type="bibr">44</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1998–1999</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Saudi Arabia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">515</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sputum smear conversion rates at the end of 3 months of treatment in patients with any rifampicin resistance or with multidrug resistance were inferior to those of patients with sensitive strains (89.8% vs. 96.3%, <italic>p</italic>
= 0.016 and 80% vs. 96.3%, <italic>p</italic>
= 0.008, respectively).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MODERATE</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Samman et al. [<xref rid="B45-ijerph-17-01395" ref-type="bibr">45</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1993–1999</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Saudi Arabia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">147</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The prevalence of poor compliance and multiply drug-resistant Mycobacterium tuberculosis were found to be significantly higher among those with treatment failure than among those in whom treatment was successful.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anuwatnonthakate et al. [<xref rid="B46-ijerph-17-01395" ref-type="bibr">46</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2004–2008</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Thailand</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9736</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cox regression analysis showed a significantly higher risk of death among patients with rifampicin resistance (adjusted hazard ratio (aHR) 1.9, 95% confident interval (CI), 1.5–2.5) and isoniazid monoresistance (aHR 1.4, 95% CI 1.1–1.7) than those with pan-susceptible group.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Deepa et al. [<xref rid="B47-ijerph-17-01395" ref-type="bibr">47</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2011</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">India</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1947</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective record review</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Of 144 INH resistant cases, 64 (44%) had poor treatment outcomes (25 (17%) default, 22 (15%) death, 12 (8%) failure and 5 (3%) transfer out) as compared to 287 (31%) among INH sensitive cases [aRR 1.46; 95% CI (1.19–1.78)].</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Báez-Saldaña et al. [<xref rid="B48-ijerph-17-01395" ref-type="bibr">48</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1995–2010</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Southern Mexico</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1243</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38–45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00–10.84).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nagu et al. [<xref rid="B49-ijerph-17-01395" ref-type="bibr">49</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2010–2011</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tanzania</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1365</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A multicentre, prospective observational study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Isoniazid resistance [relative risk (RR) = 6.0; 95% CI = 1.9–18.7; <italic>p</italic>
< 0.01] was an independent predictor of poor treatment outcomes.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Karo B et al. [<xref rid="B50-ijerph-17-01395" ref-type="bibr">50</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2002–2014</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">European Union/European Economic Area</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">194948</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Treatment success was lower among INH mono-resistant cases (Odds ratio (OR): 0.7; 95% confidence interval (CI): 0.6–0.9; adjusted absolute difference in treatment success: 5.3%).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">García-García et al. [<xref rid="B51-ijerph-17-01395" ref-type="bibr">51</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1995–1998</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Southern Mexico</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2525</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Patients with multi–drug-resistant TB had a significantly poorer prognosis than patients with fully susceptible strains or with other resistant strains (<italic>p</italic>
= 0.03).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">García-García et al. [<xref rid="B52-ijerph-17-01395" ref-type="bibr">52</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1995–1999</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mexico</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">387</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cox-adjusted relative risks showed that MDR (RR 2.5, 95%CI 1.02–6.16, <italic>p</italic>
= 0.04)was associated with mortality, controlling for age.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">García-García et al. [<xref rid="B53-ijerph-17-01395" ref-type="bibr">53</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1995–1999</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Southern Mexico</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">371</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Patients with drug resistance had a higher probability of treatment failure (OR = 16.9, CI 95% 4.5–63.0) and patients with MDR strains had a higher probability of need of re-treatment (RR = 24.4, CI 95% 8.8–67.6), and of death (RR = 4.0, CI 95% 1.5–10.7).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Noeske et al. [<xref rid="B54-ijerph-17-01395" ref-type="bibr">54</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1997–1998</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cameroon</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">560</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">332 of the 410 patients (81%) with DS-TB were cured, compared to 109/150 (72.7%) patients with DR-TB (odds ratio [OR] = 0.62, 95% confidence interval [CI] 0.40–0.99). Seven patients (1.7%) failed treatment in the DS-TB group vs. 9 (6.0%) in the DR-TB group (OR = 3.67, 95% CI 1.23–11.18). No significant difference was found in rates of death, default or transfer.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Toungoussova et al. [<xref rid="B55-ijerph-17-01395" ref-type="bibr">55</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1999</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Russia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">235</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The high rates of death (16.7%) and failure (66.7%) among patients infected with multidrug-resistant strains illustrate the negative impact of multidrug resistance on the outcome of tuberculosis treatment. Pan-resistance was significantly associated with treatment failure (<italic>p</italic>
< 0.001).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ohkado et al. [<xref rid="B56-ijerph-17-01395" ref-type="bibr">56</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2000</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Philippines</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">457</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional survey & cohort analysis of treatment</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Over 90% of the new cases, either pan-susceptible or mono-resistant, were successfully treated with the standard regimen, but four of nine MDR new cases could not be cured.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cox et al. [<xref rid="B57-ijerph-17-01395" ref-type="bibr">57</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2001–2002</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Uzbekistan</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">213</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective observational study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mortality was high, with an average of 15% (95% confidence interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible cases and 43% of 55 MDR TB cases also died per year).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Matos et al. [<xref rid="B58-ijerph-17-01395" ref-type="bibr">58</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2001–2003</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Brazil</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">396</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">An association was found between resistance and mortality from tuberculosis (adjusted OR: 7.13; 95%CI: 2.25–22.57; <italic>p</italic>
< 0.001).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Seddon et al. [<xref rid="B59-ijerph-17-01395" ref-type="bibr">59</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2003–2009</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">South Africa</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">142</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Multidrug-resistant tuberculosis (adjusted odds ratio: 12.4 [95% confidence interval: 1.17–132.3]; <italic>p</italic>
= 0.037) was a risk factor for unfavorable outcome, and multidrug-resistant tuberculosis remained a risk for death (adjusted odds ratio: 63.9 [95% confidence interval: 4.84–843.2]; <italic>p</italic>
= 0.002).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sun et al. [<xref rid="B60-ijerph-17-01395" ref-type="bibr">60</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2010</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">China</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">234</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nine years after the diagnosis of TB, 69 or 29.5% of the 234 patients had died (32 or 21.6% of non-MDR-TB versus 37 or 43.0% of MDR-TB) and the overall mortality rate was 39/1000 per year (PY) (27/1000 PY among non-MDR versus 63/1000 PY among MDR-TB).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sun et al. [<xref rid="B61-ijerph-17-01395" ref-type="bibr">61</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2010</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">China</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">250</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The mean time for recurrence among MDR-TB patients was 5.7 years, compared to 7.2 years among non-MDR-TB patients.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lockman et al. [<xref rid="B62-ijerph-17-01395" ref-type="bibr">62</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1998</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Estonia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">103</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective observational study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MDR tuberculosis (hazard ratio [HR], 7.8; 95% CI, 1.6–37.4) was associated with death due to tuberculosis in multivariable analysis.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quy et al. [<xref rid="B63-ijerph-17-01395" ref-type="bibr">63</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1998–2000</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Vietnam</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2293</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Failure was associated with multidrug resistance (adjusted odds ratios [aOR] 49.6 and 16.6, respectively) and combined resistance to isoniazid (INH) and streptomycin (SM) (aOR 13.4 and 4.8)</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pradipta et al. [<xref rid="B64-ijerph-17-01395" ref-type="bibr">64</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2005–2015</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Netherlands</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10303</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Among all DR-TB cases, patients with Multi Drug-Resistant Tuberculosis (MDR-TB) (OR 4.43; 95% CI 1.70–11.60) were more likely to have unsuccessful treatment.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Eyob et al. [<xref rid="B65-ijerph-17-01395" ref-type="bibr">65</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1999–2001</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ethiopia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">490</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Among HIV-infected TB patients who died during follow-up, survival time in those with a resistant Mycobacterium tuberculosis strain was significantly shorter compared to those with a sensitive strain (6 vs. 13 months).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sungkanuparph et al. [<xref rid="B66-ijerph-17-01395" ref-type="bibr">66</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1999–2004</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Thailand</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">225</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">INH resistance, RMP resistance and MDR-TB were associated with shorter survival (log-rank test, <italic>p</italic>
< 0.005). MDR-TB (hazard ratio [HR] 11.7; 95% CI 2.1–64.9) was significant risk factors for death.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mak et al. [<xref rid="B67-ijerph-17-01395" ref-type="bibr">67</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2003 & 2004</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">155 countries</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">121 countries</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ecologic study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Among countries using one of two standardized initial regimens, failure rates averaged 5.0%, and relapse rates averaged 12.8% in the 20 countries where prevalence of initial multidrug resistance exceeded 3%, compared with an average of 1.6% (<italic>p</italic>
< 0.0001) and 8.1% (<italic>p</italic>
= 0.0002), respectively, in 83 countries where initial multidrug resistance prevalence was less than 3%.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Falzon et al. [<xref rid="B68-ijerph-17-01395" ref-type="bibr">68</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1980–2009</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">31 centres</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Meta-analysis</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (<italic>n</italic>
= 4763; 64%, 95% CI 57–72%) or with resistance to second-line injectable drugs only (<italic>n</italic>
= 1130; 56%, 95% CI 45–66%), than in those having resistance to fluoroquinolones alone (<italic>n</italic>
= 426; 48%, 95% CI 36–60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (<italic>n</italic>
= 405; 40%, 95% CI 27–53%).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MODERATE</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HIV </td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Harrigan et al. [<xref rid="B69-ijerph-17-01395" ref-type="bibr">69</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1996–1997</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Canada</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">297</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">prospective cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Patients classified as resistant to either drug using either method had median decreases in plasma viral load of 0.05 log10 HIV RNA copies/mL or less, compared to >0.8 log10 for those with sensitive virus.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Kuritzkes et al. [<xref rid="B70-ijerph-17-01395" ref-type="bibr">70</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2008</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">220</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A case-cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The risk of virologic failure for subjects with baseline NNRTI resistance was higher than that for subjects without such resistance (hazard ratio 2.27 [95% confidence interval], 1.15–4.49; <italic>p</italic>
= 0.018).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Taniguchi et al. [<xref rid="B71-ijerph-17-01395" ref-type="bibr">71</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2001–2009</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">801</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance was associated with a 1.5-fold increased risk of virologic failure.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Simen et al. [<xref rid="B72-ijerph-17-01395" ref-type="bibr">72</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2005</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">491</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The risk of VF was higher for those who had an NNRTI-resistance mutation detected by both methods (hazard ratio [HR], 12.40 [95% confidence interval {CI}, 3.41–45.10]) and those who had mutation(s) detected only with ultra-deep sequencing (HR, 2.50 [95% CI, 1.17–5.36]).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Miller et al. [<xref rid="B73-ijerph-17-01395" ref-type="bibr">73</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1998</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Germany</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">43</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">After adjustment for all variables, phenotypic resistance to zidovudine remained the only significantly associated factor of therapy response.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Derdelinckx et al. [<xref rid="B74-ijerph-17-01395" ref-type="bibr">74</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2000</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Belgium</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">93</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">In a multivariate logistic model, controlled for log VL and CD4 count at treatment start, the association of transmitted resistance with treatment failure remained significant (OR: 148, 95% CI: 3.34- > 999.9, <italic>p</italic>
= 0.027).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lai et al. [<xref rid="B75-ijerph-17-01395" ref-type="bibr">75</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2000–2010</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Taiwan</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1349</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Matched case-control study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Compared with regimens with GSS >2.5, initiation of regimens with GSS ≤2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, <italic>p</italic>
= 0.02) and shorter time to treatment failure (log-rank <italic>p</italic>
< 0.001).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zaccarelli et al. [<xref rid="B76-ijerph-17-01395" ref-type="bibr">76</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1999–2003</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Italy</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">623</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Observational, longitudinal cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Kaplan-Meier analyses for end-points at 48 months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7, 13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively, for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new AIDS event/death.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cozzi-Lepri et al. [<xref rid="B77-ijerph-17-01395" ref-type="bibr">77</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2003–2007</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">UK</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8229</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7–22.9) in patients with no evidence of virological failure and 53% (39.3–66.7) in those with virological failure and mutations to three drug classes (<italic>p</italic>
= 0.0001)</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>NR, not reported.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="ijerph-17-01395-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">ijerph-17-01395-t003_Table 3</object-id>
<label>Table 3</label>
<caption><p>Characteristics of included studies on economic outcomes due to AMR.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author by Disease</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Year</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Site</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Sample Size</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Design/Method</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcome</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Quality Assessment</th>
</tr>
</thead>
<tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Malaria</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Phillips et al. [<xref rid="B78-ijerph-17-01395" ref-type="bibr">78</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1996</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Simplifying assumptions and illustrative calculations</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The use of quinine versus chloroquine as first-line therapy in 150 million patients with malaria would increase spending by as much as $100 million.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lubell et al. [<xref rid="B79-ijerph-17-01395" ref-type="bibr">79</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2014</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">All malaria-endemic areas</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Decision tree model</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tuberculosis</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pooran et al. [<xref rid="B80-ijerph-17-01395" ref-type="bibr">80</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2011</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">South Africa</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cost analysis</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Assuming adherence to national DR-TB management guidelines, the per patient cost of XDR-TB was $26,392, four times greater than MDR-TB ($6772), and 103 times greater than drug-sensitive TB ($257).</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pichenda et al. [<xref rid="B81-ijerph-17-01395" ref-type="bibr">81</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2011</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cambodia</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">277</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional survey</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The mean total household cost for TB patients was $477, compared to $1525 in MDR-TB cases.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">White et al. [<xref rid="B82-ijerph-17-01395" ref-type="bibr">82</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1996–1999</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">UK</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The mean cost of managing a case of pulmonary MDR TB was in excess of 60,000 pounds sterling and for sensitive disease it was 6040 pounds sterling.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rouzier et al. [<xref rid="B83-ijerph-17-01395" ref-type="bibr">83</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2007</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ecuador</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">118</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-sectional survey</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Among 104 non-MDR-TB patients, total TB-related patient costs averaged US$960 per patient, compared to an average total cost of US$6880 for 14 participating MDR-TB patients.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Marks et al. [<xref rid="B84-ijerph-17-01395" ref-type="bibr">84</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2005–2007</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">98</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Population-based study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Average hospitalization cost per XDR-TB patient (US$285,000) was 3.5 times that per MDR-TB patient (US$81,000), in 2010 dollars</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Marks et al. [<xref rid="B85-ijerph-17-01395" ref-type="bibr">85</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2005–2007</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">USA</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">135</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrospective study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HIV</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Krentz et al. [<xref rid="B86-ijerph-17-01395" ref-type="bibr">86</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2007–2011</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Canada</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">An observational cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Patients with no resistance had mean PPPM costs of CDN 1058, by contrast with the CDN 1291 costs of patients with secondary/acquired resistance. Mean costs for one, two or three ARV class resistance was CDN 1278, 1337 and 1801, respectively.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STRONG</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Martin S. [<xref rid="B87-ijerph-17-01395" ref-type="bibr">87</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2007</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Total annual costs ranged from $31 700 for a patient on a 1st-line highly active antiretroviral therapy (HAART) regimen to $42,600 on 6th-line.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Meenan RT. [<xref rid="B88-ijerph-17-01395" ref-type="bibr">88</xref>
]</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2010</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Total mean healthcare costs were $35,000 higher for patients on a 3rd- or greater line treatment regimen compared to patients on a 1st- or 2nd-line treatment regimen.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">WEAK</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>NR, not reported.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="ijerph-17-01395-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">ijerph-17-01395-t004_Table 4</object-id>
<label>Table 4</label>
<caption><p>Strength of evidence by topic.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Malaria</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Tuberculosis</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">HIV Infection</th>
</tr>
</thead>
<tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Public health outcome</td>
<td align="center" valign="middle" rowspan="1" colspan="1">+++</td>
<td align="center" valign="middle" rowspan="1" colspan="1">+++</td>
<td align="center" valign="middle" rowspan="1" colspan="1">+</td>
</tr>
<tr><td align="center" valign="middle" rowspan="1" colspan="1">Clinical outcome</td>
<td align="center" valign="middle" rowspan="1" colspan="1">+++</td>
<td align="center" valign="middle" rowspan="1" colspan="1">+++</td>
<td align="center" valign="middle" rowspan="1" colspan="1">+++</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Economic outcome</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+++</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">++</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>+ reported in one moderate evidence article, or multiple weak evidence articles; ++ reported in one strong evidence article, or multiple moderate evidence articles; +++ reported in multiple strong evidence articles.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>
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