GSK Medicine: Not applicable Study No.: 113564 (EPI-HAV-003 BOD MX) Title: Sero-prevalence of Hepatitis A, Varicella-Zoster virus, Cytomegalovirus, Herpes Simplex and Bordetella pertussis in Mexico. Rationale: The aim of this study was to document the epidemiological changes in the sero-prevalence of Hepatitis A Virus (HAV), Herpes Simplex Virus Types 1 and 2 (HSV-1 and -2), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV) and Bordetella pertussis (BP) infections in Mexico, using the National Health and Nutrition Survey (ENSANUT 2006). Objectives: Primary objective To determine sero-prevalence of HAV, CMV, VZV, HSV and BP infections in Mexico. Secondary objectives To determine the sero-prevalence of HAV, CMV, VZV, HSV and BP according to socioeconomic status (SES), age group, gender, region and risk group (including but not only: medical history, sexual behaviours, education, pregnancy history). To evaluate pertussis vaccination history on BP antibody levels among different age groups. To identify asymptomatic carriers of BP across Mexican population. Indication: Prevalence of HAV, CMV, VZV, HSV and BP infections in Mexico in subjects aged 1 to 70 years Study Investigators/Centers: GSK conducted study - 1 center in Mexico. Research Methods: Data Source: Data and serum samples collected through the ENSANUT 2006. Study Design: Cross-sectional study Study Population: Random sample of subjects aged 1 to 70 years who participated in the 2006 ENSANUT, with previously obtained informed consent. Study Exposures, Outcomes: This summary presents results for all subjects included in this study (random sample of subjects who participated in the 2006 ENSANUT). Primary outcomes Anti-HAV seropositivity status. - Subjects with anti-hav antibody titers assay cut-off. Anti-Pertussis Toxin seropositivity status for Immunoglobulin G (IgG) and Immunoglobulin A (IgA)*. - Subjects with anti-pertussis Toxin antibody titers assay cut-off for IgG. - Subjects with anti-pertussis Toxin antibody titers assay cut-off for IgA*. Anti-VZV seropositivity status. - Subjects with anti-vzv antibody titers assay cut-off. Anti-CMV seropositivity status. - Subjects with anti-cmv antibody titers assay cut-off. Anti-HSV seropositivity status (defined as the percentage of subjects with anti-hsv 1 and 2 titers assay cut-off). - Subjects with anti-hsv antibody titers assay cut-off. Secondary outcomes Difference in HAV, CMV, VZV, HSV and BP seropositivity rates according to the following parameters: - Area - Region - - Gender - Socioeconomic stratum - Risk groups (including but not only: medical history, sexual behaviours, education, pregnancy history) - Pertussis vaccination status* *Anti-Pertussis Toxin IgA were not assessed. *Data only available for children (1-9 years) Data Analysis Methods: The analyses were performed on the According-To-Protocol (ATP) Cohort. - The ATP Cohort included all evaluable subjects (i.e., those meeting all eligibility criteria, complying with the procedures defined in the protocol). 1
The number of subjects seropositive for anti-hav, anti-vzv, anti-cmv, antihsv-1, anti-hsv-2 and anti-bp was tabulated for all the subjects. Chi-square test (or Fisher's exact test depending on the case) was performed to compare the difference in every single disease (HAV, BP, VZV, CMV and HSV) of seroprevalence between the areas, genders, age-strata, regions and socioeconomic groups separately. Descriptive statistics were provided for risk factor in every single disease. The percentage of subjects who were seropositive for anti-bp antibodies was also stratified by pertussis vaccination status, in children (1-9 years). Limitations: Not applicable Study Results: Demographics/Baseline Characteristics Study Group Planned, N 4000 N (ATP Cohort) 3658 Mean, years (SE) 29.0 (0.6) Females:Males 1968:1686 Primary Outcome Measure: Percentage of subjects seropositive for anti-hav, anti-vzv, anti-cmv, anti-hsv antibodies and anti-bp antibodies (ATP Cohort) Antibodies n Seropositive 95% CI N % LL UL Anti-HAV 2890 81616.8 84.2 81.7 86.7 Anti-VZV 2882 81848.4 85.8 83.6 87.9 Anti-CMV 3094 86543.9 89.2 87.4 91.1 Anti-HSV 1 2652 78175.0 80.9 78.3 83.4 Anti-HSV 2 232 9531.0 9.9 7.9 12.0 Anti-BP IgG 1515 42340.4 47.4 43.0 51.9 95%CI = exact 95% two-sided confidence interval LL = lower limit UL= upper limit Seropositivity was defined as below: Anti-HAV: - < 1.00 = nonreactive - > 1.00 = reactive Anti-VZV: - < 0.1 = negative - > 0.2 = positive Anti-CMV: - < 6 = nonreactive - > 6 = reactive Anti-HSV 1 & anti-hsv 2 (qualitative results): - IgG positive - IgG negative Anti-BP IgG: - < 11 = negative - > 11 = positive Secondary Outcome Measure: Difference in HAV, VZV, CMV, HSV, BP sero-prevalence between areas (ATP Cohort) N Rural Urban P-value n N % N N % Anti-HAV 81616.8 1469 35340.1 86.9 1421 46276.7 82.2 0.0523 Anti-VZV 81848.4 1333 31877.9 80.3 1549 49970.5 89.7 <.0001 Anti-CMV 86543.9 1522 36766.2 90.4 1572 49777.7 88.4 0.3035 Anti-HSV 1 78175.0 1338 33471.2 82.5 1314 44703.8 79.7 0.265 Anti-HSV 2 9531.0 98 2835.9 7.1 134 6695.1 12.0 0.0072 Anti-BP IgG 42340.4 695 18215.3 48.9 820 24125.1 46.4 0.5565 2
Secondary Outcome Measure: Difference in HAV, VZV, CMV, HSV, BP sero-prevalence between regions (ATP Cohort) N Center District Federal North South P- value n N % n N % n N % n N % Anti-HAV 81616.8 960 23197.7 85.6 103 14465.7 78.8 835 17924.5 80.8 992 26029.0 88.8 0.0234 Anti-VZV 81848.4 958 22741.7 85.1 130 16691.0 91.1 936 19543.9 89.5 858 22871.8 80.1 0.0009 Anti-CMV 86543.9 1014 24622.6 90.8 130 16196.9 88.2 904 18770.0 84.6 1046 26954.4 91.9 0.0357 Anti-HSV 1 78175.0 895 22033.6 81.3 109 15078.7 82.4 801 17441.1 79.3 847 23621.7 80.6 0.8984 Anti-HSV 2 9531.0 66 1783.9 6.6 20 3001.1 16.4 67 2241.9 10.2 79 2504.0 8.8 0.0178 Anti-BP IgG 42340.4 490 11124.4 46.5 85 7194.9 39.5 469 11132.1 54.1 471 12889.0 48.4 0.1918 Secondary Outcome Measure: Difference in HAV, VZV, CMV, HSV and BP sero-prevalence between age strata (ATP Cohort) N Children (1-9) Adolescent (10-19) Adult ( 20) P- value n N % n N % n N % Anti-HAV 81616.8 572 7835.6 45.0 1426 15671.2 80.1 892 58110.1 96.9 <.0001 Anti-VZV 81848.4 632 9825.8 57.5 1406 16220.7 84.4 844 55801.9 94.4 <.0001 Anti-CMV 86543.9 784 12210.6 70.1 1429 16109.5 82.4 881 58223.8 97.0 <.0001 Anti-HSV 1 78175.0 583 8461.2 48.8 1221 13856.4 71.1 848 55857.4 93.3 <.0001 Anti-HSV 2 9531.0 23 451.6 2.6 51 565.9 2.9 158 8513.4 14.4 <.0001 Anti-BP IgG 42340.4 544 9465.2 59.3 590 7388.3 40.4 381 25487.0 46.3 0.0008 Secondary Outcome Measure: Difference in HAV, VZV, CMV, HSV, BP sero-prevalence between genders (ATP Cohort) N Female Male P-value n N % n N % Anti-HAV 81616.8 1603 42617.1 86.1 1287 38999.7 82.2 0.1021 Anti-VZV 81848.4 1577 42122.5 86.8 1305 39725.9 84.6 0.2621 Anti-CMV 86543.9 1706 44366.2 89.6 1388 42177.7 88.8 0.689 Anti-HSV 1 78175.0 1488 40947.2 82.8 1164 37227.8 78.8 0.1143 Anti-HSV 2 9531.0 153 6454.3 13.2 79 3076.7 6.6 0.0011 Anti-BP IgG 42340.4 768 18476.7 41.4 747 23863.7 53.4 0.0007 Secondary Outcome Measure: Difference in HAV, VZV, CMV, HSV, BP sero-prevalence between SES (ATP Cohort) N Low Medium High P-value n N % n N % n N % Anti-HAV 77412.8 1720 42882.1 86.6 841 28147.8 82.0 66 6383.0 90.1 0.0546 Anti-VZV 77599.2 1630 40397.5 83.0 908 30438.6 90.0 85 6763.1 97.1 <.0001 Anti-CMV 81591.8 1792 44226.4 89.3 933 30989.2 90.3 78 6376.2 90.0 0.9209 Anti-HSV 1 74334.5 1534 40449.5 81.8 803 27685.6 80.8 65 6199.3 88.7 0.3362 3
Anti-HSV 2 9127.6 114 4139.3 8.5 97 4478.7 13.1 7 509.6 7.2 0.1398 Anti-BP IgG 38808.2 861 21557.6 47.9 443 15168.1 48.1 40 2082.6 29.7 0.0808 Secondary Outcome Measure: Risk factors for anti-hav seropositive subjects (ATP Cohort) N= 96982 Characteristics Parameters or n N % 95% CI Chi- P-value Unad 95% CI LL UL Square. OR LL UL Children (1-9 years) Vs Adult ( 20 years) 572 7835.6 45.0 39.4 50.5 86.7104 <.0001 0.0 0.0 0.1 Adolescent (10-19 years) 1426 15671.2 80.1 76.7 83.6 0.6445 0.4221 0.1 0.0 0.4 Gender Female Vs Male 1603 42617.1 86.1 83.3 88.9 2.6377 0.1044 1.3 0.9 1.9 Area Urban Vs Rural 1421 46276.7 82.2 78.4 86.0 3.7926 0.0515 0.7 0.5 1.0 Region Center 960 23197.7 85.6 81.9 89.3 1.0 District Federal 103 14465.7 78.8 70.7 86.8 2.9325 0.0868 0.6 0.4 1.1 North 835 17924.5 80.8 74.2 87.4 1.3628 0.2431 0.7 0.4 1.2 South 992 26029.0 88.8 86.5 91.0 11.3176 0.0008 1.3 0.9 1.9 SES Low Vs High 1720 42882.1 86.6 83.8 89.5 0.0015 0.9686 0.7 0.4 1.3 Medium Vs High 841 28147.8 82.0 77.0 86.9 5.103 0.0239 0.5 0.3 1.0 Chronic disease status Diabetes present Vs 49 2660.4 87.4 72.1 100 2.0185 0.1554 0.3 0.0 1.7 (for adults) Have you ever smoked/ consumed tobacco * Yes Vs No 157 14587.7 97.4 93.5 100 0.0032 0.9549 1.1 0.1 9.2 Yes Vs No 174 14004.7 99.7 99.1 100 7.0828 0.0078 22.0 2.3 214.7 UL= Upper Limit Secondary Outcome Measure: Risk factors for anti-vzv seropositive subjects (ATP Cohort) N= 95440 Characteristics Parameters or n N % 95% CI Chi- P- Unad. 95% CI LL UL Square value OR LL UL Children (1-9 years) 632 9825.8 57.5 51.9 63.1 129.6422 <.0001 0.1 0.0 0.1 Adolescent (10-19 1406 16220.7 84.4 81.8 87.0 0.7868 0.3751 0.3 0.2 0.5 years) Vs Adult ( 20 years) Gender Female Vs Male 1577 42122.5 86.8 84.4 89.3 1.2482 0.2639 1.2 0.9 1.6 Area Urban Vs Rural 1549 49970.5 89.7 87.5 91.9 20.226 <.0001 2.1 1.5 3.0 Region Center 958 22741.7 85.1 81.2 89.1 1.0 District Federal 130 16691.0 91.1 86.1 96.0 3.041 0.0812 1.8 0.9 3.5 North 936 19543.9 89.5 86.8 92.2 2.7931 0.0947 1.5 1.0 2.3 South 858 22871.8 80.1 76.0 84.2 13.846 0.0002 0.7 0.5 1.1 4
SES Low Vs High 1630 40397.5 83.0 79.9 86.0 22.0333 <.0001 0.1 0.1 0.4 Medium Vs High 908 30438.6 90.0 87.0 93.0 1.6506 0.1989 0.3 0.1 0.7 Chronic disease status (in adults) Diabetes present Vs 52 3045.6 100 100 100 1622.1357 <.0001 >999.999 >999.999 >999.999 Have you ever Yes Vs No 152 14161.9 94.8 90.2 99.4 0.872 0.3505 2.3 0.4 13.9 smoked/consumed tobacco * Yes Vs No 160 13290.0 94.6 91.2 98.1 0.025 0.8741 1.1 0.4 3.1 UL= Upper Limit Secondary Outcome Measure: Risk factors for anti-cmv seropositive subjects (ATP Cohort) N= 96982 Characteristics Parameters or n N % 95% CI Chi- P- Unad. 95% CI LL UL Square value OR LL UL Children (1-9 years) 784 12210.6 70.1 64.0 76.1 68.3833 <.0001 0.1 0.0 0.1 Adolescent (10-19 1429 16109.5 82.4 79.4 85.3 12.1333 0.0005 0.1 0.1 0.2 years) Vs Adult ( 20 years) Gender Female Vs Male 1706 44366.2 89.6 87.1 92.1 0.1602 0.6889 1.1 0.7 1.6 Area Urban Vs Rural 1572 49777.7 88.4 85.8 91.0 1.0786 0.299 0.8 0.6 1.2 Region Center 1014 24622.6 90.8 88.3 93.4 1.0 District Federal 130 16196.9 88.2 81.3 95.0 0.1463 0.7021 0.8 0.4 1.6 North 904 18770.0 84.6 80.8 88.5 7.357 0.0067 0.6 0.4 0.8 South 1046 26954.4 91.9 90.0 93.8 5.3084 0.0212 1.1 0.8 1.7 SES Low Vs High 1792 44226.4 89.3 86.5 92.1 0.0837 0.7723 0.9 0.3 2.5 Chronic disease status (in adults) Have you ever smoked/consumed tobacco * Medium Vs High 933 30989.2 90.3 87.7 92.8 0.0477 0.8271 1.0 0.4 2.9 Diabetes present Vs 52 3045.6 100 1971.0875 <.0001 >999.999 >999.999 >999.999 Yes Vs No 157 14653.1 97.8 95.0 100 0.1936 0.66 1.6 0.2 12.9 Yes Vs No 172 13852.5 98.6 96.9 100 2.2447 0.1341 3.0 0.7 12.9 5
UL= Upper Limit Secondary Outcome Measure: Risk factors for anti-hsv type 1 seropositive subjects (ATP Cohort) N= 96683 Characteristics Parameters or n N % 95% CI Chi- P-value Unad. 95% CI LL UL Square OR LL UL Children (1-9 years) Vs Adult ( 20 years) Adolescent (10-19 years) Vs Adult ( 20 years) 583 8461.2 48.8 43.2 54.4 107.39 53 <.0001 0.2 0.1 0.3 1221 13856.4 71.1 67.8 74.3 6.0934 0.0136 0.1 0.0 0.1 Gender Female Vs Male 1488 40947.2 82.8 79.7 85.9 2.4677 0.1162 1.3 0.9 1.8 Area Urban Vs Rural 1314 44703.8 79.7 75.8 83.6 1.2659 0.2605 0.8 0.6 1.1 Region Center 895 22033.6 81.3 76.9 85.7 1.0 District Federal 109 15078.7 82.4 74.8 90.1 0.2257 0.6348 1.1 0.6 2.0 North 801 17441.1 79.3 73.3 85.4 0.4001 0.527 0.9 0.6 1.4 South 847 23621.7 80.6 77.6 83.7 0.0309 0.8604 1.0 0.7 1.4 SES Low Vs High 1534 40449.5 81.8 78.9 84.7 0.9936 0.3189 0.6 0.2 1.3 Medium Vs High 803 27685.6 80.8 75.8 85.9 1.7658 0.1839 0.5 0.2 1.2 Chronic disease status (in adults) Diabetes present Vs 50 3002.0 98.6 96.4 100 4.5694 0.0325 6.1 1.2 32.2 Have you ever smoked/consum ed tobacco * Yes Vs No 151 14317.1 95.6 91.0 100 0.448 0.5033 1.6 0.4 7.0 Yes Vs No 165 13548.5 96.5 93.2 99.8 3.1548 0.0757 3.0 0.9 9.8 UL= Upper Limit Secondary Outcome Measure: Risk factors for anti-hsv type 2 seropositive subjects (ATP Cohort) N= 95813 Characteristics Parameters or n N % 95% CI Chi- P-value Unad. 95% CI LL UL Square OR LL UL Children (1-9 years) Vs 23 451.6 2.6 1.3 4.0 11.0357 0.0009 0.2 0.1 0.3 Adult ( 20 years) Adolescent (10-19 years) 51 565.9 2.9 1.8 4.0 10.078 0.0015 0.2 0.1 0.3 Gender Female Vs Male 153 6454.3 13.2 10.0 16.3 10.2608 0.0014 2.2 1.3 3.4 Area Urban Vs Rural 134 6695.1 12.0 8.7 15.2 7.3406 0.0067 1.8 1.2 2.7 Region Center 66 1783.9 6.6 4.1 9.1 1.0 District Federal 20 3001.1 16.4 7.7 25.1 4.8669 0.0274 2.8 1.3 5.9 North 67 2241.9 10.2 6.4 14.0 0.0155 0.9008 1.6 0.9 2.9 South 79 2504.0 8.8 6.4 11.1 0.8118 0.3676 1.4 0.8 2.2 6
SES Low Vs High 114 4139.3 8.5 6.2 10.8 0.1872 0.6653 1.2 0.4 3.9 Medium Vs High 97 4478.7 13.1 8.9 17.3 2.7169 0.0993 1.9 0.6 6.3 Chronic disease Diabetes present Vs 19 1019.7 33.5 13.4 53.6 6.3885 0.0115 3.5 1.3 9.1 status (in adults) Have you ever Yes Vs No 26 2117.9 14.2 6.1 22.3 0.004 0.9493 1.0 0.4 2.7 smoked/consumed tobacco * Yes Vs No 27 2115.5 15.2 7.0 23.3 0.095 0.7579 1.1 0.5 2.3 UL= Upper Limit Secondary Outcome Measure: Risk factors for BP IgG seropositive subjects (ATP Cohort) N= 89306 Characteristics Parameters or n N % 95% CI Chi- P- Unad. 95% CI LL UL Square value OR LL UL Children (1-9 years) Vs 544 9465.2 59.3 52.6 66.0 16.083 <.0001 1.7 1.2 2.5 Adult ( 20 years) Adolescent (10-19 years) 590 7388.3 40.4 36.9 43.9 14.792 0.0001 0.8 0.6 1.1 Gender Female Vs Male 768 18476.7 41.4 36.5 46.4 10.908 0.001 0.6 0.5 0.8 Area Urban Vs Rural 820 24125.1 46.4 39.8 52.9 0.338 0.5612 0.9 0.6 1.3 Region Center 490 11124.4 46.5 40.0 53.1 1.0 District Federal 85 7194.9 39.5 24.6 54.5 1.589 0.2075 0.8 0.4 1.5 North 469 11132.1 54.1 48.1 60.1 4.664 0.0308 1.4 0.9 1.9 South 471 12889.0 48.4 42.7 54.1 0.169 0.6812 1.1 0.8 1.5 SES Low Vs High 861 21557.6 47.9 43.2 52.6 2.341 0.126 2.2 0.9 5.1 Medium Vs High 443 15168.1 48.1 41.2 54.9 2.868 0.0903 2.2 1.0 5.0 Chronic disease Diabetes present Vs 24 1539.1 51.8 28.2 75.4 0.226 0.6346 1.3 0.5 3.5 status (in adults) Have you ever smoked/consum ed tobacco * Yes Vs No 74 6321.0 43.5 29.3 57.8 0.123 0.7261 0.8 0.3 2.2 Yes Vs No 70 5348.8 40.0 27.0 53.1 1.494 0.2216 0.7 0.4 1.3 7
UL= Upper Limit Secondary Outcome Measure: Percentage of subjects who are seropositive for anti-bp antibodies stratified by pertussis vaccination status, in children (1-9 years) (ATP Cohort) Antibodies Pertussis vaccination status Seropositive 95% CI n N % LL UL Anti-BP IgG Vaccinated 89 3516.6 67.5 57.8 77.3 Not vaccinated 1 2.4 2.2 0.0 8.3 95%CI = exact 95% two-sided confidence interval LL = lower limit UL= upper limit Conclusion: The sero-prevalence of HAV, CMV, VZV, HSV-1, HSV-2 and BP infections in Mexico was 84.2%, 89.2%, 85.8%, 80.9%, 9.9% and 47.4%, respectively. Publications: Lazcano-Ponce E et al. Seroprevalence of bordetella pertussis antibodies in Mexican Population: A cross-sectional study. Abstract presented at the 51st Annual Interscience Conference on Antimicrobial nts & Chemotherapy (ICAAC). Berlin, Germany, 17-22 September 2011. Effelterre TV et al. Model-based projections of the population-level impact of Hepatitis A vaccination in Mexico. Abstract presented at the Excellence In Paediatrics (EIP). Istanbul, Turkey, 30 November-3 December 2011. Date updated: 10-April-2012 8