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RANDOMIZED TRIALS IN CHILD HEALTH IN DEVELOPING COUNTRIES, 2012-2013, VACCINES AND IMMUNIZATION

Wednesday, 21st of May 2014

Randomised trials in child health in developing countries 2012-2013, Vaccines and immunization, pp. 181-200.

 

The following abstracts form part of a larger document summarizing RCTs on child health in developing countries, accessible online at

http://www.ichrc.org/sites/www.ichrc.org/files/RCTs%20in%20child%20health%20in%20developing%20countries%202012-13.pdf

BCG vaccine

 

No effect of oral polio vaccine administered at birth on mortality and  immune response to BCG. A natural experiment. Lund N ,  Andersen A ,  Monteiro I ,  Aaby P ,  Benn CS . Vaccine. 2012 Oct 19;30(47):6694 - 9. doi: 10.1016/j.vaccine.2012.08.055. Epub 2012 Sep 6. Source Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum  Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. najaaraq@dadlnet.dk

 

Abstract

BACKGROUND:  WHO recommends oral polio vaccine at birth (OPV0) in polio endemic  countries . During a  period without OPV in  Guinea - Bissau in 2004, w e observed that not receiving OPV0 was  associated with significantly decreased mortality in boys and better immune response to BCG  vaccination. In 2007, whilst conducting a  trial of BCG and vitamin A supplementation (VAS) at  birth to low birthweight (LBW)  children , OPV was again lacking for a short period. We used  this natural experiment to test the previous observations.

 

METHODS:  In the  trial LBW infants were randomised to early or delayed BCG and VAS or placebo at  birth. We noted whether the  children received OPV0 or not. We compared  children who  received No OPV0 with those who received OPV0 in the 2 months before and the 2 months  after the period without OPV. Mortality was compared in Cox regression models providing  adjusted hazard ratios (aHR); the immune response to BCG was assessed in Poisson models  providing adjusted prevalence ratios (aPR).

 

RESULTS:  Ninety - nine  children received No OPV0 and were compared with 243  children who received  OPV0.  No OPV0 was associated with insignificantly higher mortality during the first year  of life, the aHR being 1.83 (95% CI: 0.93 - 3.61). The effect was similar in boys and girls.  Overall, there was no significant association between No OPV0 and having a positive PPD  response (aPR=1.33 (0.64 - 2.78)) or a scar (aPR=1.02 (0.93 - 1.11)) after BCG vaccination,  though No OPV0 boys were more likely to develop a scar (aPR: 1.10 (1.01 - 1.20)).

 

CONCLUSIONS:  The findings did not support our previous observation that not receiving OPV0 was  associated with reduced mortality in boys.  The findings weakly supported that OPV0 leads to  a dampened response to simultaneously administered BCG vaccine in boys.

 

Diphtheria - Tetanus - Pertussis vaccine

 

Diphtheria - tetanus - pertussis vaccination administered after measles  vaccine: increased female mortality? Benn CS ,  Aaby P . Pediatr Infect Dis J. 2012 Oct;31(10):1095 - 7. doi: 10.1097/INF.0b013e318263135e. Source Bandim Health Project, Research Center for Vitamins and Vaccines, Statens Serum Institut,  Copenhagen S, Denmark. cb@ssi.dk

 

Abstract

In low - income  countries ,  children should receive 3 doses of diphtheria - tetanus - pertussis vaccine  (DTP) at 6, 10 and 14 weeks of age, and measles vaccine at 9 months of age. However, there is  often a delay in administering the vaccines, and DTP is often given after measles vaccine.  Previous observations suggest that this practice is associated with increased mortality for  female, but not for male  children . Within a vitamin A  trial in  Guinea - Bissau, vaccination status  was registered at the time of measles vaccination at 9 months; 141 (31%) of 455  children were  missing 1 or more DTP vaccines and were likely to receive them afterward. We examined  whether missing DTP vaccine at this time point was associated with sex - differential effects on  mortality. In female  children , missing DTP was associated with 3.55 (95% confidence interval:  1.23 - 10.26) times higher risk of dying before 36 months of age,  whereas it made no difference  in male  children (0.97 [0.34 - 2.80]). The result supports that receiving DTP after measles vaccine  affects female  children negatively. Comment This study adds to many observations by the same group over 2 decades. Confounding could  have played a role in the results of this non - randomised trial . For example, children with  incomplete DTP vaccination could have been delayed in receiving the  routine vaccinations  because the child had been sick , or the family had poor care seeking behaviour , putting them at  higher risk of death .  The authors note that although both boys and girls with incomplete DTP  vaccinations had lower nutritional status at enrolment than those who were fully vaccinated,  this is unlikely to explain  the  observe d large  difference in mortality in female children,  nor  would it explain why there was no effect in male children. The order that vaccines are given  seems to have an effect on high mortality populations, independent of the disease they are  designed to protect against.

 

Dengue vaccine

 

Immunogenicity and safety of recombinant tetravalent dengue vaccine  (CYD - TDV) in individuals aged 2 - 45 y: Phase II  randomized controlled  trial in Singapore. Leo YS ,  Wilder - Smith A ,  Archuleta S ,  Shek LP ,  Chong CY ,  Leong HN ,  Low CY,  Oh ML ,  Bouckenooghe A ,  Wartel TA ,  Crevat D . Hum Vaccin Immunother. 2012 Sep;8(9):1259 - 71. doi: 10.4161/hv.21224. Epub 201 2 Aug 16.

 

Source Tan Tock Seng Hospital; Singapore.

 

Abstract

This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore.  The  primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV)  comprising four recombinant, live, attenuated viruses (CYD - TDV) and the dengue virus  serotype - specific antibody responses before and 28 d after each vaccination . Participants  were  randomized 3:1 to receive three doses of CYD - TDV or a control vaccine at 0, 6 and 12  mo. Control vaccine was placebo for the first dose (all ages) and for subsequent doses, licensed  hepatitis - A for  children (aged 2 - 11 y) or influenza vaccine for adolescents (12 - 17 y) and adults  (18 - 45 y). Between April and October 2009, 317  children, 187 adolescent s and 696 adults were  enrolled . In all age groups, reactogenicity was higher after the first injection of CYD - TDV  than after placebo control. Reactogenicity after subsequent CYD - TDV doses was no  higher than after the first dose, and tended to be lower or s similar to that seen after active  control vaccination. Seropositivity rates and geometric mean neutralizing antibody titers  (GMTs; 1/dil) against all four dengue virus serotypes increased in all age groups after each of  the three CYD - TDV doses. Post - dose 3, 66.5% of all participants were seropositive to all four  serotypes, and 87.2% were seropositive to ≥ 3 serotypes; GMTs for all participants ranged from  43.0 against dengue virus serotype 1 to 100 against dengue virus serotype 4. GMTs were higher  in  children n than in adolescents . These results support the continued development of CYD - TDV for the prevention of dengue disease.  

 

Immunogenicity and safety of tetravalent dengue vaccine in 2 - 11 year - olds previously vaccinated against yellow fever:  randomized ,  controlled , phase II study in Piura, Peru. Lanata CF ,  Andrade T ,  Gil AI ,  Terrones C ,  Valladolid O ,  Zambrano B ,  Saville M ,  Crevat D . Vaccine. 2012 Sep 7;30(41):5935 - 41. doi: 10.1016/j.vaccine.2012.07.043. Epub 2012 Jul 31 Source Instituto de Investigacion Nutricional, Av. La Molina 1885, La Molina Lima - 12, Peru.

 

Abstract

In a  randomized , placebo - controlled , monocenter, observer blinded study conducted in an area  where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live,  attenuated, tetravalent dengue vaccine candidate (CYD - TDV) in 2 - 11 year - olds with varying  levels of pre - existing yellow - fever immunity due to vaccination 1 - 7 years previously.  199  children received 3 injections of CYD - TDV (months 0, 6 and 12) and 99 received placebo  (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the  third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of  178 - 190 (1/dil) (versus 16.7 - 38.1 in the control group), a 10 - 20 fold - increase from baseline, and  94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There  were no vaccine - related SAEs. The observed reactogenicity profile was consistent with phase I  studies, with severity grade 1 - 2 injection site pain, headache, malaise and fever most frequently  reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases  were seen after completion of the 3 doses: 1 in the CYD - TDV group (N=199), and 3 in the  control group (N=99).  A 3 - dose regimen of CYD - TDV had a good safety profile in 2 - 11 year  olds with a history of YF vaccination and elicited robust antibody y responses that were  balanced against the four serotypes HPV vaccine

HPV

Human papillomavirus vaccination in Tanzanian schoolgirls: cluster - randomized trial comparing 2 vaccine - delivery strategies. Watson - Jones D ,  Baisle y K ,  Ponsiano R ,  Lemme F ,  Remes P ,  Ross D ,  Kapiga S ,  Mayaud P ,  de  Sanjosé S ,  Wight D ,  Changalucha J ,  Hayes R . J Infect Dis. 2012 Sep 1;206(5):678 - 86. doi: 10.1093/infdis/jis407. Epub 2012 Jun 18. Source London School of Hygiene and Tropical Medicine, London, UK. deborah.watson - jones@lshtm.ac.uk

 

Abstract

 

BACKGROUND:  We compared vaccine coverage achieved by 2 different delivery strategies for the quadrivalent  human papillomavirus (HPV) vaccine in Tanzanian schoolgirls.

 

METHODS:  In a cluster - randomized trial of HPV vaccination conducted in Tanzania a, 134 primary schools  were randomly assigned to class - based (girls enrolled in primary school grade [class] 6) or age - based (girls born in 1998; 67 schools per arm) vaccine delivery. The primary outcome was  coverage by dose.

 

RESULTS:  There were 3352 and 2180 eligible girls in schools  randomized to class - based and age - based delivery, respectively. HPV vaccine coverage was 84.7% for dose 1, 81.4% for dose  2, and 76.1% for dose 3. For each dose, coverage was higher in class - based schools than in  age - based s schools (dose 1: 86.4% vs 82.0% [P = .30]; dose 2: 83.8% vs 77.8% [P = .05];  and dose 3: 78.7% vs 72.1% [P = .04]). Vaccine - related adverse events were rare. Reasons for  Randomised trials in child  health in developing countries 2012 - 13 185 not vaccinating included absenteeism (6.3%) and parent refusal (6.7%). School absenteeism  rates prior to vaccination ranged from 8.1% to 23.5%.

 

CONCLUSIONS:  HPV vaccine can be delivered with high coverage in schools in sub - Saharan  Africa . Compared  with age - based vaccination, class - based vaccination located more eligible pupils and achieved higher coverage. HPV vaccination did not increase absenteeism rates in selected schools.  Innovative strategies will be needed to reach out - of - school girls.

 

 

Reasons for receiving or not receiving HPV vaccination in primary  schoolgirls in Tanzania: a case control study. Watson - Jones D ,  Tomlin K ,  Remes P ,  Baisley K ,  Ponsiano R ,  Soteli S ,  de Sanjosé S ,  Changalucha J ,  Kapiga S ,  Hayes RJ . PLoS One. 2012;7(1 0):e45231. doi: 10.1371/journal.pone.0045231. Epub 2012 Oct 24. Source London School of Hygiene and Tropical Medicine, London, United Kingdom. Deborah.Watson - Jones@lshtm.ac.uk

 

Abstract

 

BACKGROUND:  There are few data on factors influencing human papillomavirus (HPV) vaccination uptake in  sub - Saharan  Africa . We examined the characteristics of receivers and non - receivers of HPV  vaccination in Tanzania and identified reasons for not receiving the vaccine.

 

METHODS:  We conducted a case control study of HPV v vaccine receivers and non - receivers within a phase  IV cluster - randomised  trial of HPV vaccination in 134 primary schools in Tanzania. Girls who  failed to receive vaccine (pupil cases) and their parents/guardians (adult cases) and girls who  received dose 1 ( pupil controls) of the quadrivalent vaccine (Gardasil™) and their  parents/guardians (adult controls) were enrolled from 39 schools in a 1 ∶ 1 ratio and interviewed  about cervical cancer, HPV vaccine knowledge and reasons why they might have received or  not received the vaccine. Conditional logistic regression was used to determine factors  independently associated with not receiving HPV vaccine.

 

RESULTS:  We interviewed 159 pupil/adult cases and 245 pupil/adult controls.  Adult - factors  independently associated with a daughter being a case were older age, owning fewer  household items, not attending a school meeting about HPV vaccine, and not knowing  anyone with cancer. Pupil - factors for being a case included having a non - positive opinion  about the school de - worming programme, poor knowledge about the location of the cervix,  and not knowing that a vaccine could prevent cervical cancer. Reasons for actively  refusing vaccination included concerns about side effects and infertility.  Most adult and  pupil cases reported that they would accept the HPV vaccine if it were offered again (97% and  93% respectively). Randomised trials in child  health in developing countries 2012 - 13 186

 

CONCLUSIONS:  Sensitisation messages, especially targeted at older and poorer parents, knowledge  retention and parent meetings are critical for vaccine acceptance e in Tanzania. Vaccine side  effects and fertility concerns should be addressed prior to a national vaccination program.  Parents and pupils who initially decline vaccination should be given an opportunity to  reconsider their decision.

 

 

Influenza vaccine

Design and initiation of a study to assess the direct and indirect effects  of influenza vaccine given to  children in rural  India . Sullender W ,  Fowler K ,  Krishnan A ,  Gupta V ,  Moulton LH ,  Lafond K ,  Widdowson MA ,  Lal  RB ,  Broor S . ##  Vaccine. 2012 Jul 27;30(35):5235 - 9. doi: 10.1016/j.vaccine.2012.06.002. Epub 2012 Jun 16 Source University of Alabama Birmingham, Birmingham, AL, USA. wsull@me.com

 

Abstract

 

The burden of disease due to influenza is not well characterized for  children in  developing  countries and the effectiveness of available influenza vaccines in lower resource settings has not  been established.  We initiated a prospective, longitudinal, phase IV, household - randomized ,  control led , observer - blinded three year study (2009 - 2011) in a rural community of  India to  measure the total and indirect household protective effects of immunizing  children ages 6  months through 10 years with seasonal inactivated trivalent influenza vaccine (TIV ) or a  control vaccine (n=3697). Active weekly surveillance was conducted year round with home  visits for identification of febrile acute respiratory illness (FARI) conducted for all vaccine  recipients and household members (n=18,220). Nasal and throat swabs were collected from each  FARI episode for influenza detection by real - time reverse transcription polymerase chain  reaction. The primary outcome was reduction in laboratory confirmed influenza infections in the  influenza vaccine versus control vaccine group, with secondary outcome assessing indirect  effects among the entire study population. This report describes the study site, cluster study  design, choice of study and control vaccines, and the initial enrolment in the study.  

 

Safety and immunogenicity of an adjuvanted whole virion, inactivated  A (H1N1) 2009 influenza vaccine in young and elderly adults, and  children .

 

Abstract

 

BACKGROUND:  Approximately 826, 000  children , mostly young infants, die annually from invasive  pneumococcal disease. A 6 - 10 - 14 - week schedule of pneumococcal conjugate vaccine (PCV) is  efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted  an open  randomized controlled trial in  Papua New Guinea to compare safety, immunogenicity  and priming for memory of 7 - valent PCV (PCV7) given in a 0 - 1 - 2 - month (neonatal) schedule  with that of the routine 1 - 2 - 3 - month (infant) schedule.

 

METHODS:  We  randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or  no PCV7.  All infants received 23 - valent pneumococcal polysaccharide vaccine (PPV) at age 9  months.  Serotype - specific serum IgG for PCV7 (VT) serotypes and non - VT serotypes 2, 5  and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age.  Primary outcomes  were geometric mean concentrations (GMCs) and proportions with concentration ≥ 0.35 μg/ml  of VT serotype - specific pneumococcal IgG at age 2 months and one month post - PPV.

 

RESULTS:  We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control  groups. Despite high background levels of maternally derived antibody, both PCV7 groups  had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05)  and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were  significantly higher (p<0.001) at age 2 months in the neonatal (one month post - dose2  PCV7) than in the infant group (one month post - dose1 PCV7). PPV induced significantly  higher VT antibody responses in PCV7 - primed than unprimed infants, with neonatal and infant  groups equivalent. High VT and non - VT antibody concentrations generally persisted to age 18  months.

 

CONCLUSIONS:  PCV7 is well - tolerated and immunogenic in PNG neonates and young infants and induces  immunologic memory to PPV booster at age 9 months with antibody levels maintained to  age 18 months.

 

 

Effect of age and vaccination with a pneumococcal conjugate vaccine  on the density of pneumococcal nasopharyngeal carriage. Roca A ,  Bottomley C ,  Hill PC ,  Bojang  A ,  Egere U ,  Antonio M ,  Darboe O ,  Greenwood BM ,  Adegbola RA . Clin Infect Dis. 2012 Sep;55(6):816 - 24. doi: 10.1093/cid/cis554. Epub 2012 Jun 14. Source Medical Research Council Unit, Gambia. aroca@mrc.gm

 

Abstract

 

BACKGROUND:  This study evaluated the impact of age and pneumococcal vaccination on the density of  pneumococcal nasopharyngeal carriage.

 

METHODS:  A cluster - randomized trial was conducted in rural Gambia.  In 11 villages (the vaccine group),  all residents received 7 - valent pneumococcal conjugate vaccine (PCV - 7), while in another  10 villages (the control group), only  children <30 months old or born during the study  period received PCV - 7. Cross - sectional surveys (CSSs) were conducted to collect  nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after  vaccination. Pneumococcal density was defined using a semiquantitative classification (range,  1 - 4) among colonized individuals. An age - trend analysis of density was conducted using data  from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before  and after vaccination.

 

RESULTS:  Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine - type (VT) and non - vaccine - type (NVT) pneumococci; it decreased with age (P < .001 for VT  and NVT). There was a decrease  in the density of VT carriage following vaccination in  individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from  2.57 to 2.11; P = .070) in the vaccinated villages.  Similar decreases in density were observed  with NVT within vaccinated and control villages. No significant differences were found  between vaccinated and control villages in the postvaccination comparisons for either VT  or NVT.

 

CONCLUSIONS:  A high density of carriage among young subjects might partly explain  why  children are more  efficient than adults in pneumococcal transmission.  PCV - 7 vaccination lowered the density of  VT and of NVT pneumococcal carriage in the before - after vaccination analysis. Clinical  Trials Registration: ISRCTN51695599.

 

Comment: Pneumococcal conjugate vaccine may have a protective herd immunity effect by reduction in  density of nasopharyngeal carriage and reduced transmission. What is surprising in this study  is the observed decrease in non - vaccine strains after vaccination.  This component of the study  was a before - and - after comparison, making it possible that secular trends or other confounding  influenced the results . This finding remains unexplained, and is counter - intuitive to other  studies that indicate serotype replacement with non - vaccine serotypes is common (including  the same research groups below, in neonates).

 

 

Indirect effect of 7 - valent pneumococcal conjugate vaccine on  pneumococcal carriage in newborns in rural Gambia: a randomised  controlled trial . Egere U ,  Townend J ,  Roca A ,  Akinsanya A ,  Bojang A ,  Nsekpong D ,  Greenwood B ,  Adegbola  RA ,  Hill PC . PLoS One. 2012;7(11):e49143. doi: 10.1371/journal.pone. 0049143 Epub 2012 Nov 21. Source Medical Research Council Unit, Banjul, The Gambia. uegere@mrc.gm

 

Abstract

 

BACKGROUND:  Gambian infants frequently  acquire Streptococcus pneumoniae soon after birth. We investigated  the indirect effect of 7 - valent pneumococcal conjugate vaccine (PCV - 7) on pneumococcal  acquisition in newborn Gambian babies.

 

METHODS:  Twenty - one villages were randomised to receive PCV - 7 to all subjects (11 vaccinated villages)  or to infants aged 2 - 30 months (10 control villages). Other control villagers received  Meningococcal C conjugate vaccine. From 328 babies born during the  trial , nasopharyngeal  swabs were collected after birth, then weekly until 8 weeks of age when they received their first  dose of PCV - 7. Pneumococcal carriage and acquisition rates were compared between the study  arms and with a baseline study.

 

RESULTS:  57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both  arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT)  (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non - vaccine  serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/14 4], p = 0.246).  Infants from vaccinated  villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26 - 0.58], p<0.001) and  increased acquisition of NVT (HR 1.16 [0.87 - 1.56], p = 0.312). VT carriage (51.6% vs.  37.5%, p = 031 in control and 46.1% v s. 16.8%, p<0.001 in vaccinated villages) and acquisition  rates (HR 0.68 [0.50 - 0.92], p = 0.013 in control villages and HR 0.31 [0.19 - 0.50], p<.001 in  vaccinated villages) were significantly lower in both study arms than in the baseline study.  NVT  carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in  vaccinated villages) and acquisition rates (HR 1.48 [1.06 - 2.06], p = 0.022) and (HR 1.52  [1.11 - 2.10], p = 0.010 respectively) were significantly higher.

 

CONCLUSION:  PCV - 7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect  effect likely originated from both the  child and adult vaccinated populations.  Increased  carriage of NVT pneumococci needs ongoing monitoring.

 

 

Immunogenicity and Safety of a 13 - Valent Pneumococcal Conjugate  Vaccine in Healthy Infants and Toddlers Given with Routine Vaccines  in  India . Amdekar YK ,  Lalwani SK ,  Bavdekar A ,  Balasubramanian S ,  Chhatwal J ,  Bhat SR ,  Verghese  VP ,  Tansey SP ,  Gadgil D ,  Jiang Q ,  Pride M ,  Emini EA ,  Gruber WC ,  Scott DA . Pediatr Infect Dis J. 2012 Nov 28. [Epub ahead of print] Randomised trials in child  health in developing countries 2012 - 13 195 Source From the *Consultant Pediatrician, Jaslok Hospital and Research Center, Mumbai,  India ;  †Bharati Vidyapeeth University Medical College Pune,  India ; ‡Department of Pediatrics, K. E.  M. Hospital Research Centre, Rasta Peth, Pune,  India ; §Kanchi Kamakoti CHILDS Trust  Hospital and The CHILDS Trust Medical Research Foundation, Nungambakkam, Chennai,  India ; ¶Christian Medical College & Hospital, Ludhiana, Punjab,  India ; ║Department of  Pediatrics, St. Johns Medical College, Bangalore,  India ; **Department of  Child Health,  Christian Medical College, Vellore,  India ; ††Pfizer Inc, Maidenhead, United Kingdom; ‡‡Pfizer  Pharmaceutical  India Pvt. Ltd; §§Pfizer Inc, Collegeville, Pennsylvania; ¶¶Pfizer Inc, Pearl  River,  New York.

 

Abstract

 

BACKGROUND:: The  childhood burden of disease due to Streptococcus pneumoniae is  particularly high in  India .  The immunogenicity and safety of 13 - valent pneumococcal  conjugate vaccine (PCV13) was compared with 7 - valent pneumococcal conjugate vaccine  (PCV7) in a  randomized , active - controlled , double - blind  trial conducted at 12 sites in  India .

 

METHODS: Healthy infants received PCV13 or PCV7 at 6, 10, and 14 weeks of age  (infant series), and 12 months of age (toddler dose) along with routine pediatric vaccinations.  Immunoglobulin G responses against the 13 pneumococcal serotypes were evaluated 1 month  after the infant series and posttoddler dose. Pertussis and poliomyelitis immune responses were  assessed 1 month after the infant series. Safety and tolerability were also assessed.

 

RESULTS:  The immunogenicity results for the 7 common serotypes and the concomitant vaccines  (whole - cell pertussis and oral poliovirus) were similar for subjects receiving PCV13 and  subjects receiving PCV7. Immune responses t o the 6 additional serotypes were higher in  the PCV13 group compared with the PCV7 group. PCV13 and PCV7 had similar safety  and tolerability profiles.

 

CONCLUSIONS: PCV13 has similar immunogenicity to PCV7 in  response to the 7 common serotypes, and generally higher immunogenicity in response to the 6  additional serotypes. PCV13 may provide added protection against pneumococcal disease  caused by the additional 6 serotypes, and does not interfere with immune responses to whole - cell pertussis and oral poliovirus vaccines. PCV13 has an acceptable safety profile in both  infants and toddlers, comparable to that of PCV7. Immunogenicity and safety of 10 - valent pneumococcal non - typeable 

 

 

Haemophilus influenzae protein D - conjugate vaccine (PHiD - CV) co - administered with routine  childhood vaccines in Taiwan. Lin TY ,  Lu CY ,  Chang LY ,  Chiu CH ,  Huang YC ,  Bock HL ,  Tang H ,  François N ,  Moreira M ,  Schuerman L ,  Huang LM . J Formos Med Assoc. 2012 Sep;111(9):495 - 503. doi: 10.1016/j.jfma.2011.07.014. Epub 2012  Mar 18. Source Chang Gung  Children s Hospital, Chang Gung University College of Medicine, Taiwan.

 

Abstract

 

BACKGROUND/PURPOSE: The immunogenicity and safety of the 10 - valent pneumococcal nontypeable Haemophilus  influenzae (H. Influenzae) protein D conjugate vaccine (PHiD - CV), co - administered with  routine  childhood vaccines, were assessed in Taiwanese infants.

 

METHODS:  In this open study, 230 healthy infants were primed with three doses of PHiD - CV (Synflorix)  and diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and  Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa - HBV - IPV/Hib vaccine) at 1.5, 3  and 6 months of age and two doses of oral human rotavirus vaccine at 1.5 and 3 months.  Pneumococcal immune responses were assessed 1 month post - dose three, by 22F - inhibition  ELISA and opsonophagocytic activity (OPA) assay. Local and general soli cited/unsolicited  symptoms and serious adverse events (SAEs) were recorded.

 

RESULTS:  At least 95.4% of participants had an antibody concentration ≥ 0.2 μg/mL against each  vaccine serotype. At least 96.1% of participants had an OPA titer ≥ 8 against each vaccine  serotype except 6B (87.3%). All infants, but one, were seropositive for antibodies against  nontypeable H. influenzae protein D. Immune responses to the co - administered vaccines were  good and in line with previous reports. PHiD - CV was well tolerate d, with low (≤ 6.3%)  incidences of grade 3 solicited local symptoms. The frequencies of general symptoms were in  line with other pneumococcal conjugate vaccine studies. There were no systematic increases in  incidences of solicited general or local symptoms with successive doses. There were no reports  of grade 3 fever (rectal temperature > 40 °C) or SAEs considered to be causally related to  vaccination.

 

CONCLUSION:  PHiD - CV co - administered with routine  childhood vaccines within the first 6 months of  life, was highly immunogenic, and well tolerated in Taiwanese infants.

 

Rotavirus vaccine Vaccines for preventing rotavirus diarrhoea: vaccines in use. Soares - Weiser K ,  Maclehose H ,  Bergman H ,  Ben - Aharon I ,  Nagpal S ,  Goldberg E ,  Pitan F ,  Cunliffe N . Cochrane Database Syst Rev. 2012 Nov 14;11:CD008521. doi:  10.1002/14651858.CD008521.pub3. Source Enhance Reviews Ltd,Wantage, UK.  karla@enhance - reviews .com

 

Abstract

 

BACKGROUND:  Rotavirus results in more diarrhoea - related deaths in  children less than five years of age than  any other single agent in  countries with high  childhood mortality. It is also a common cause of  Randomised trials in child  health in developing countries 2012 - 13 197 diarrhoea - related hospital admissions in  countries with low  childhood mortality. Currently  licensed rotavirus vaccines include a monovalent rotavirus vaccine (RV1; Rotarix,  GlaxoSmithKline Biologicals) and a pentavalent rotavirus vaccine (RV5; RotaTeq, Merck &  Co., Inc.). Lanzhou lamb rotavirus vaccine (LLR; Lanzhou Institute of Biomedical Products) is  used in China only.

 

OBJECTIVES:  To evaluate rotavirus vaccines approved for use (RV1, RV5, and LLR) for preventing rotavirus  diarrhoea. SEARCH METHODS:  We searched MEDLINE (via PubMed) (19 66 to May 2012), the Cochrane Infectious Diseases  Group Specialized Register (10 May 2012), CENTRAL (published in The Cochrane Library  2012, Issue 5), EMBASE (1974 to 10 May 2012), LILACS (1982 to 10 May 2012), and BIOSIS  (1926 to 10 May 2012). We also searched the ICTRP (10 May 2012), www.ClinicalTrials.gov  (28 May 2012) and checked reference lists of identified studies.

 

SELECTION CRITERIA:  We selected  randomized controlled trials (RCTs) in  children comparing rotavirus vaccines  approved for use with placebo, no intervention, or another vaccine.

 

DATA COLLECTION AND ANALYSIS:  Two authors independently assessed  trial eligibility, extracted data, and assessed risk of bias.  We combined dichotomous data using the risk ratio (RR) and 95% confidence intervals ( CI).  We stratified the analysis by  child mortality, and used GRADE to evaluate evidence quality.

 

MAIN RESULTS:  Forty - one trials met the inclusion criteria and enrolled a total of 186,263 participants. Twenty - nine trials (101,671 participants) assessed RV 1, and 12 trials (84,592 participants)  evaluated RV5. We did not find any trials assessing LLR.RV1Children aged less than one year:  In  countries with low - mortality rates, RV1 prevents 86% of severe rotavirus diarrhoea cases  (RR 0.14, 95% CI 0.07 to 0.26; 4 0,631 participants, six trials; high - quality evidence), and, based  on one large multicentre  trial in Latin  America and Finland, probably prevents 40% of severe  all - cause diarrhoea episodes (rate ratio 0.60, 95% CI 0.50 to 0.72; 17,867 participants, one  trial ;  moderate - quality evidence).  In  countries with high - mortality rates, RV1 probably prevents  63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.18 to 0.75; 5414 participants,  two trials; moderate - quality evidence), and, based on one  trial in Malawi and  South Africa , 34% of severe all - cause diarrhoea cases (RR 0.66, 95% CI 0.44 to 0.98; 4939  participants, one  trial ; moderate - quality evidence) . Children aged up to two years: In  countries with low - mortality rates, RV1 prevents 85% of severe rotavirus diarrhoea cases (RR  0.15, 95% CI 0.12 to 0.20; 32,854 participants, eight trials; high - quality evidence), and probably  37% of severe all - cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091  participants, two trials; moderate - quality evidence).  In  countries with high - mortality rates,  based on one  trial in Malawi and  South Africa , RV1 probably prevents 42% of severe  rotavirus diarrhoea cases (RR 0.58, 95% CI 0.42 to 0.79; 2764 participants, one  trial ;  moderate - quality evidence), and 18% of severe all - cause diarrhoea cases (RR 0.82, 95%  CI 0.71 to 0.95; 2764 participants, one  trial ; moderate - quality evidence) .RV5Children aged  less than one year: In  countries with low - mortality rates, RV5 probably prevents 87% of severe  rotavirus diarrhoea cases (RR 0.13, 95% CI 0.04 to 0.45; 2344 participants, three trials;  moderate - quality evidence), and, based on one  trial in Finland, may prevent 72% of severe all - cause diarrhoea cases (RR 0.28, 95% CI 0.16 to 0.48; 1029 participants, one  trial ; low - quality  Randomised trials in child  health in developing countries 2012 - 13 198 evidence ). In  countries with high - mortality rates, RV5 prevents 57% of severe rotavirus  diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, two trials; high - quality  evidence), but there was insufficient data to assess the effect on severe all - cause  diarrhoea. Children aged up to two years: Four studies provided data for severe rotavirus and  all - cause diarrhoea in  countries with low - mortality rates. Three trials reported on severe  rotavirus diarrhoea cases and found that RV5 probably prevents 82% (RR 0. 18, 95% CI 0.07 to  0.50; 3190 participants, three trials; moderate - quality evidence), and another  trial in Finland  reported on severe all - cause diarrhoea cases and found that RV5 may prevent 96% (RR 0.04,  95% CI 0.00 to 0.70; 1029 participants, one  trial ;  low - quality evidence). In high - mortality  countries , RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82;  5885 participants, two trials; high - quality evidence), and 15% of severe all - cause diarrhoea  cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, two trials; high - quality evidence). There  was no evidence of a vaccine effect on mortality (181,009 participants, 34 trials; low - quality evidence), although the trials were not powered to detect an effect on this endpoint. Serious adverse events were reported in 4565 out of 99,438  children vaccinated with RV1  and in 1884 out of 78,226  children vaccinated with RV5. Fifty - eight cases of intussusception  were reported in 97,246  children after RV1 vaccination, and 34 cases in 81,459  children after  RV5 vaccination. No significant difference was found between  children receiving RV1 or RV5  and placebo in the number of serious adverse events, and intussusception in particular.

 

AUTHORS CONCLUSIONS:  RV1 and RV5 prevent episodes of rotavirus diarrhoea. The vaccine efficacy is lower in  high - mortality  countries ; however, due to the higher burden of disease, the absolute  benefit is higher in these settings.  No increased risk of serious adverse events including  intussusception was detected, but post - introduction surveillance studies are required to detect  rare events associated with vaccination.

 

 

Human rotavirus vaccine Rotarix™ provides protection against diverse  circulating rotavirus strains in African infants: a  randomized controlled  trial . Steele AD ,  Neuzil KM ,  Cunliffe NA ,  Madhi SA ,  Bos P ,  Ngwira B ,  Witte D ,  Todd S ,  Louw C ,  Kirsten M ,  Aspinall S ,  Van Doorn LJ ,  Bouckenooghe A ,  Suryakiran PV ,  Han HH . BMC Infect Dis. 2012 Sep 13;12:213. doi: 10.1186/1471 - 2334 - 12 - 213. Source Rotavirus Vaccine Program, PATH, 2201 Westlake Ave, Seattle, WA 98121, USA.  duncan.steele@gatesfoundation.org

 

Abstract

 

BACKGROUND:  Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in  children <5 years of age. The human, G1P[8] rotavirus vaccine Rotarix™ significantly reduced severe  rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in  South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus  Randomised trials in child  health in developing countries 2012 - 13 199 gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered  during the first rotavirus - seas on.

 

METHODS:  Healthy infants aged 5 - 10 weeks were enrolled and  randomized into three groups to  receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the  pooled Rotarix™ group) or three doses of placebo at a 6,10,14 - week schedule.  Weekly  home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by  ELISA and genotyped by RT - PCR and nucleotide sequencing. The percentage of infants with  severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post - last  dose until one year of age and the corresp onding vaccine efficacy was calculated with 95% CI.

 

RESULTS:  Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443)  were included in the per protocol efficacy cohort. G1 wild - type was detected in 23 (1.6%)  severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of  detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo).  Vaccine efficacy  against G1 wild - type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95%  CI: - 6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the  predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis  cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in  placebo) and P[6] (13 [0.9%] in placebo).  Vaccine  efficacy against P[8] was 59.1% (95% CI:  32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5; 87.0%) and P[6] was 55.2% (95% CI:  - 6.5%; 81.3%)

 

CONCLUSIONS:  Rotarix™ vaccine demonstrated efficacy against severe gastroenteritis caused by diverse  circulating rotavirus types. These data add to a growing body of evidence supporting  heterotypic protection provided by Rotarix™.  

 

 

Typhoid vaccine

 

Effectiveness of Vi capsular polysaccharide typhoid vaccine among  children : a cluster  randomized trial in Karachi, Pakistan. Khan MI ,  Soofi SB ,  Ochiai RL ,  Habib MA ,  Sahito SM ,  Nizami SQ ,  Acosta CJ ,  Clemens JD ,  Bhutta ZA ;  DOMI Typhoid Karachi Vi Effectiveness Study Group . Collaborators (12) Khan MJ ,  Memon Z ,  Puri MK ,  Kim DR ,  Park JK ,  You Y ,  Ali M ,  Choi SY ,  Alam D ,  Hasan R ,  Zafar A ,  Donner A . Vaccine. 2012 Aug 3;30(36):5389 - 95. doi: 10.1016/j.vaccine.2012.06.015. Epub 2012 Jun 18. Randomised trials in child  health in developing countries 2012 - 13 200 Source International Vaccine Institute, Seoul, Republic of Korea.

 

Abstract

BACKGROUND:  Typhoid  fever is endemic in Karachi, with an incidence among  children ranging from 170 to  450 per 100,000  child - years. Vaccination strategies are important for prevention, and the Vi capsular polysaccharide (ViCPS) vaccine has been shown to be effective in reducing the burden  of typhoid fever.

 

METHODS:  A cluster  randomized trial was conducted in three low socioeconomic urban squatter settlements  in Karachi, Pakistan between 2002 and 2007. Subsamples were followed up for assessment of  immune response and adverse events after vaccination.

 

RESULTS:  The study participants were similar in a wide variety of socio - demographic and economic  characteristics at baseline.  A total of 27,231 individuals of the total target population of  51,965 in 120 clusters either received  a ViCPS vaccine (13,238 [52% coverage]) or the  control Hepatitis A vaccine (13,993 [53%]). Typhoid fever was diagnosed in 30 ViCPS  vaccine recipients and 49 Hepatitis A vaccine recipients with an adjusted total protective  effectiveness of 31% (95%CI:  - 28%, 63%). The adjusted total vaccine protective  effectiveness was  - 38% (95%CI:  - 192%, 35%) for  children aged 2 - 5 years and 57%  (95%CI: 6%, 81%) for  children 5 - 16 years old.

 

CONCLUSION:  The ViCPS vaccine did not confer statistically significant protection to children in the  study areas, and there was a decline in antibody response 2 years post - vaccination. However, the ViCPS vaccine showed significant total protection in  children 5 - 16 years of age,  which is consistent with other studies of ViCPS vaccine condu cted in  India , Nepal, China and  South Africa . These findings suggest that ViCPS vaccination of school - aged  children will  protect the  children of urban, typhoid endemic areas against typhoid fever.