The Effect of Tuberculosis Treatment at Combination Antiretroviral Therapy Initiation on Subsequent Mortality: A Systematic Review and Meta-Analysis

<div><p>Objective</p><p>We aimed to perform a systematic review and meta-analysis examining the impact of TB treatment at the time of combination antiretroviral therapy (cART) initiation on subsequent mortality.</p> <p>Methods</p><p>We searched PubMed, EMBASE, and selected conference proceedings for studies that report adult mortality on cART, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used to examine the influence of study and population characteristics.</p> <p>Results</p><p>22 eligible cohort studies reported data on 98,350 (range 74-15,225) adults, of whom 14,779 (15%) were receiving TB treatment at cART initiation. Studies of those receiving vs. not receiving TB treatment had an average mortality relative risk of 1.10 (95% confidence interval 0.87-1.40) at 1-3 months (based upon 8 estimates), 1.15 (0.94-1.41) at 6-12 months (11 estimates), and 1.33 (1.02-1.75) at 18-98 months (10 estimates) following cART initiation. However, there was a wide range of estimates and those at later time points were markedly heterogeneous. Meta-regression identified factors associated with elevated average risk estimates: lower median baseline CD4 counts and adjustment for baseline hemoglobin at 1-3 months; longer length of follow-up and women-only studies at 6-12 months; and not adjusting for BMI/weight at 18-98 months.</p> <p>Conclusions</p><p>Patients receiving TB treatment at cART initiation did not have a statistically significant estimated increase in short-term risk of all-cause mortality as compared to those not receiving TB treatment. TB treatment was significantly associated with increased mortality after about a year of cART, suggesting that patients with concurrent TB treatment at cART initiation may benefit from continued support after TB treatment completion.</p> </div

Identification and selection of eligible studies.

<p>Identification and selection of eligible studies.</p

Forest plot of mortality relative risks reported by 22 studies.

<p>The relative risks correspond to the estimated effect of receiving vs. not receiving TB treatment at the time of cART initiation on subsequent mortality among HIV-infected adults. Estimates are ordered according to length of follow-up time. Estimates were abstracted according to the precision used by the original authors; estimates calculated using available data are reported to 2 decimal places. Abbreviations: cART, combination antiretroviral therapy; CI, confidence interval; HIV, human immunodeficiency virus; RR, relative risk; TB, tuberculosis. </p

Global distribution of included studies.

<p>Countries are shaded if a study was included in this review.</p

Forest plot for the summary estimates of pyrazinamide prevalence by WHO region and presence or risk of MDR-TB.

<p>Abbreviations: CI, confidence interval; DST, drug susceptibility test; MDR-TB, multi-drug resistant tuberculosis; N/A, not applicable; WHO, world health organization. MDR-TB was defined as an isolate being resistant to RIF and INH. High risk of MDR-TB was defined as an isolate being resistant to at least one anti-TB drug. *Any TB was defined as the inclusion of patients independent of drug resistance profile.</p

Flow diagram describing article selection.

<p>Flow diagram describing article selection.</p

Distribution of reported single nucleotide polymorphisms (SNPs) throughout the <i>pncA</i> gene.

<p>Dashed lines indicate the open reading frame for the <i>pncA</i> gene.</p

Estimated annual burden of new PZA resistant tuberculosis cases, overall and among MDR-TB patients, globally and by WHO region.

<p>Abbreviations: MDR-TB, multi-drug resistant tuberculosis; PZA, pyrazinamide; TB, tuberculosis; WHO, World Health Organization.</p><p>* Incidence of TB cases from the World Health Organization Global Tuberculosis Report 2014.</p><p>Estimated annual burden of new PZA resistant tuberculosis cases, overall and among MDR-TB patients, globally and by WHO region.</p

Bacterial meningitis epidemiology and return of <i>Neisseria meningitidis</i> serogroup A cases in Burkina Faso in the five years following MenAfriVac mass vaccination campaign

<div><p>Background</p><p>Historically, <i>Neisseria meningitidis</i> serogroup A (NmA) caused large meningitis epidemics in sub-Saharan Africa. In 2010, Burkina Faso became the first country to implement a national meningococcal serogroup A conjugate vaccine (MACV) campaign. We analyzed nationwide meningitis surveillance data from Burkina Faso for the 5 years following MACV introduction.</p><p>Methods</p><p>We examined Burkina Faso’s aggregate reporting and national laboratory-confirmed case-based meningitis surveillance data from 2011–2015. We calculated incidence (cases per 100,000 persons), and described reported NmA cases.</p><p>Results</p><p>In 2011–2015, Burkina Faso reported 20,389 cases of suspected meningitis. A quarter (4,503) of suspected meningitis cases with cerebrospinal fluid specimens were laboratory-confirmed as either <i>S</i>. <i>pneumoniae</i> (57%), <i>N</i>. <i>meningitidis</i> (40%), or <i>H</i>. <i>influenzae</i> (2%). Average adjusted annual national incidence of meningococcal meningitis was 3.8 (range: 2.0–10.2 annually) and was highest among infants aged <1 year (8.4). <i>N</i>. <i>meningitidis</i> serogroup W caused the majority (64%) of meningococcal meningitis among all age groups. Only six confirmed NmA cases were reported in 2011–2015. Five cases were in children who were too young (n = 2) or otherwise not vaccinated (n = 3) during the 2010 MACV mass vaccination campaign; one case had documented MACV receipt, representing the first documented MACV failure.</p><p>Conclusions</p><p>Meningococcal meningitis incidence in Burkina Faso remains relatively low following MACV introduction. However, a substantial burden remains and NmA transmission has persisted. MACV integration into routine childhood immunization programs is essential to ensure continued protection.</p></div

Aggregate and case-based meningitis surveillance data indicators, Burkina Faso, 2011–2015.

<p>Aggregate and case-based meningitis surveillance data indicators, Burkina Faso, 2011–2015.</p