Interventions for improving coverage of child immunization in low- and middle-income countries.

Immunization coverage remains low, particularly in low- and middle-income countries (LMIC), despite its proven effectiveness in reducing the burden of childhood infectious diseases. A Cochrane review has shown that patient reminder recall is effective in improving coverage of immunization but technologies to support this strategy are lacking in LMIC. To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunization coverage in LMIC. We searched the following databases for primary studies: Cochrane Central Register of Controlled Trials (CENTRAL) 2010, Issue 1, part of The Cochrane Library. www.thecochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 8 July 2010); MEDLINE, Ovid (1948 to March Week 3 2011) (searched 30 March 2011); EMBASE, Ovid (1980 to 2010 Week 26) (searched 8 July 2010); CINAHL, EBSCO (1981 to present ) (searched 8 July 2010); LILACS, VHL (1982 to present) (searched 8 July 2010); Sociological Abstracts, CSA Illumnia (1952 to current) (searched 8 July 2010). Reference lists of all papers and relevant reviews were identified and searched for additional studies. Included studies were randomized controlled trials (RCTs), non-randomized controlled trials (NRCTs), and interrupted-time-series (ITS) studies. Study participants were children aged 0 to 4 years, caregivers, and health providers. Interventions included patient and community-oriented interventions, provider-oriented interventions, health system interventions, multi-faceted (any combination of the above categories of interventions), and any other single or multifaceted intervention intended to improve childhood immunisation coverage The primary outcome was the proportion of the target population fully immunized with recommended vaccines by age. Two authors independently screened full articles of selected studies, extracted data, and assessed study quality. Six studies were included in the review; four were at high risk of bias. There was low quality evidence that: facility based health education may improve the uptake of combined vaccine against diphtheria, pertussis, and tetanus (DPT3) coverage (risk ratio (RR) 1.18; 95% CI 1.05 to 1.33); and also that a combination of facility based health education and redesigned immunization cards may improve DPT3 coverage (RR 1.36; 95% CI 1.22 to 1.51). There was also moderate quality evidence that: evidence-based discussions probably improve DPT3 coverage (RR 2.17; 95% CI 1.80 to 2.61), and that information campaigns probably increase uptake of at least a dose of a vaccine (RR 1.43; 95% CI 1.01 to 2.02). Home visits and health education may improve immunization coverage but the quality of evidence is low.

Oyo-Ita A ，Nwachukwu CE ，Oringanje C ，Meremikwu MM ... -  《Cochrane Database of Systematic Reviews》

Interventions for improving coverage of childhood immunisation in low- and middle-income countries.

Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on interventions for improving childhood immunisation coverage in LMICs. To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunisation coverage in LMICs. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 4, part of The Cochrane Library. www.cochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 12 May 2016); MEDLINE In-Process and Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 12 May 2016); CINAHL 1981 to present, EbscoHost (searched 12 May 2016); Embase 1980 to 2014 Week 34, OvidSP (searched 2 September 2014); LILACS, VHL (searched 2 September 2014); Sociological Abstracts 1952 - current, ProQuest (searched 2 September 2014). We did a citation search for all included studies in Science Citation Index and Social Sciences Citation Index, 1975 to present; Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 2 July 2016). We also searched the two Trials Registries: ICTRP and ClinicalTrials.gov (searched 5 July 2016) SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT), non-RCTs, controlled before-after studies, and interrupted time series conducted in LMICs involving children aged from birth to four years, caregivers, and healthcare providers. We independently screened the search output, reviewed full texts of potentially eligible articles, assessed risk of bias, and extracted data in duplicate; resolving discrepancies by consensus. We then conducted random-effects meta-analyses and used GRADE to assess the certainty of evidence. Fourteen studies (10 cluster RCTs and four individual RCTs) met our inclusion criteria. These were conducted in Georgia (one study), Ghana (one study), Honduras (one study), India (two studies), Mali (one study), Mexico (one study), Nicaragua (one study), Nepal (one study), Pakistan (four studies), and Zimbabwe (one study). One study had an unclear risk of bias, and 13 had high risk of bias. The interventions evaluated in the studies included community-based health education (three studies), facility-based health education (three studies), household incentives (three studies), regular immunisation outreach sessions (one study), home visits (one study), supportive supervision (one study), information campaigns (one study), and integration of immunisation services with intermittent preventive treatment of malaria (one study).We found moderate-certainty evidence that health education at village meetings or at home probably improves coverage with three doses of diphtheria-tetanus-pertussis vaccines (DTP3: risk ratio (RR) 1.68, 95% confidence interval (CI) 1.09 to 2.59). We also found low-certainty evidence that facility-based health education plus redesigned vaccination reminder cards may improve DTP3 coverage (RR 1.50, 95% CI 1.21 to 1.87). Household monetary incentives may have little or no effect on full immunisation coverage (RR 1.05, 95% CI 0.90 to 1.23, low-certainty evidence). Regular immunisation outreach may improve full immunisation coverage (RR 3.09, 95% CI 1.69 to 5.67, low-certainty evidence) which may substantially improve if combined with household incentives (RR 6.66, 95% CI 3.93 to 11.28, low-certainty evidence). Home visits to identify non-vaccinated children and refer them to health clinics may improve uptake of three doses of oral polio vaccine (RR 1.22, 95% CI 1.07 to 1.39, low-certainty evidence). There was low-certainty evidence that integration of immunisation with other services may improve DTP3 coverage (RR 1.92, 95% CI 1.42 to 2.59). Providing parents and other community members with information on immunisation, health education at facilities in combination with redesigned immunisation reminder cards, regular immunisation outreach with and without household incentives, home visits, and integration of immunisation with other services may improve childhood immunisation coverage in LMIC. Most of the evidence was of low certainty, which implies a high likelihood that the true effect of the interventions will be substantially different. There is thus a need for further well-conducted RCTs to assess the effects of interventions for improving childhood immunisation coverage in LMICs.

Oyo-Ita A ，Wiysonge CS ，Oringanje C ，Nwachukwu CE ，Oduwole O ，Meremikwu MM ... -  《Cochrane Database of Systematic Reviews》

Interventions for improving coverage of childhood immunisation in low- and middle-income countries.

Immunisation plays a major role in reducing childhood morbidity and mortality. Getting children immunised against potentially fatal and debilitating vaccine-preventable diseases remains a challenge despite the availability of efficacious vaccines, particularly in low- and middle-income countries. With the introduction of new vaccines, this becomes increasingly difficult. There is therefore a current need to synthesise the available evidence on the strategies used to bridge this gap. This is a second update of the Cochrane Review first published in 2011 and updated in 2016, and it focuses on interventions for improving childhood immunisation coverage in low- and middle-income countries. To evaluate the effectiveness of intervention strategies to boost demand and supply of childhood vaccines, and sustain high childhood immunisation coverage in low- and middle-income countries. We searched CENTRAL, MEDLINE, CINAHL, and Global Index Medicus (11 July 2022). We searched Embase, LILACS, and Sociological Abstracts (2 September 2014). We searched WHO ICTRP and ClinicalTrials.gov (11 July 2022). In addition, we screened reference lists of relevant systematic reviews for potentially eligible studies, and carried out a citation search for 14 of the included studies (19 February 2020). Eligible studies were randomised controlled trials (RCTs), non-randomised RCTs (nRCTs), controlled before-after studies, and interrupted time series conducted in low- and middle-income countries involving children that were under five years of age, caregivers, and healthcare providers. We independently screened the search output, reviewed full texts of potentially eligible articles, assessed the risk of bias, and extracted data in duplicate, resolving discrepancies by consensus. We conducted random-effects meta-analyses and used GRADE to assess the certainty of the evidence. Forty-one studies involving 100,747 participants are included in the review. Twenty studies were cluster-randomised and 15 studies were individually randomised controlled trials. Six studies were quasi-randomised. The studies were conducted in four upper-middle-income countries (China, Georgia, Mexico, Guatemala), 11 lower-middle-income countries (Côte d'Ivoire, Ghana, Honduras, India, Indonesia, Kenya, Nigeria, Nepal, Nicaragua, Pakistan, Zimbabwe), and three lower-income countries (Afghanistan, Mali, Rwanda). The interventions evaluated in the studies were health education (seven studies), patient reminders (13 studies), digital register (two studies), household incentives (three studies), regular immunisation outreach sessions (two studies), home visits (one study), supportive supervision (two studies), integration of immunisation services with intermittent preventive treatment of malaria (one study), payment for performance (two studies), engagement of community leaders (one study), training on interpersonal communication skills (one study), and logistic support to health facilities (one study). We judged nine of the included studies to have low risk of bias; the risk of bias in eight studies was unclear and 24 studies had high risk of bias. We found low-certainty evidence that health education (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.15 to 1.62; 6 studies, 4375 participants) and home-based records (RR 1.36, 95% CI 1.06 to 1.75; 3 studies, 4019 participants) may improve coverage with DTP3/Penta 3 vaccine. Phone calls/short messages may have little or no effect on DTP3/Penta 3 vaccine uptake (RR 1.12, 95% CI 1.00 to 1.25; 6 studies, 3869 participants; low-certainty evidence); wearable reminders probably have little or no effect on DTP3/Penta 3 uptake (RR 1.02, 95% CI 0.97 to 1.07; 2 studies, 1567 participants; moderate-certainty evidence). Use of community leaders in combination with provider intervention probably increases the uptake of DTP3/Penta 3 vaccine (RR 1.37, 95% CI 1.11 to 1.69; 1 study, 2020 participants; moderate-certainty evidence). We are uncertain about the effect of immunisation outreach on DTP3/Penta 3 vaccine uptake in children under two years of age (RR 1.32, 95% CI 1.11 to 1.56; 1 study, 541 participants; very low-certainty evidence). We are also uncertain about the following interventions improving full vaccination of children under two years of age: training of health providers on interpersonal communication skills (RR 5.65, 95% CI 3.62 to 8.83; 1 study, 420 participants; very low-certainty evidence), and home visits (RR 1.29, 95% CI 1.15 to 1.45; 1 study, 419 participants; very low-certainty evidence). The same applies to the effect of training of health providers on interpersonal communication skills on the uptake of DTP3/Penta 3 by one year of age (very low-certainty evidence). The integration of immunisation with other services may, however, improve full vaccination (RR 1.29, 95% CI 1.16 to 1.44; 1 study, 1700 participants; low-certainty evidence). Health education, home-based records, a combination of involvement of community leaders with health provider intervention, and integration of immunisation services may improve vaccine uptake. The certainty of the evidence for the included interventions ranged from moderate to very low. Low certainty of the evidence implies that the true effect of the interventions might be markedly different from the estimated effect. Further, more rigorous RCTs are, therefore, required to generate high-certainty evidence to inform policy and practice.

Oyo-Ita A ，Oduwole O ，Arikpo D ，Effa EE ，Esu EB ，Balakrishna Y ，Chibuzor MT ，Oringanje CM ，Nwachukwu CE ，Wiysonge CS ，Meremikwu MM ... -  《Cochrane Database of Systematic Reviews》

Improving vaccination uptake among adolescents.

Adolescent vaccination has received increased attention since the Global Vaccine Action Plan's call to extend the benefits of immunisation more equitably beyond childhood. In recent years, many programmes have been launched to increase the uptake of different vaccines in adolescent populations; however, vaccination coverage among adolescents remains suboptimal. Therefore, understanding and evaluating the various interventions that can be used to improve adolescent vaccination is crucial. To evaluate the effects of interventions to improve vaccine uptake among adolescents. In October 2018, we searched the following databases: CENTRAL, MEDLINE Ovid, Embase Ovid, and eight other databases. In addition, we searched two clinical trials platforms, electronic databases of grey literature, and reference lists of relevant articles. For related systematic reviews, we searched four databases. Furthermore, in May 2019, we performed a citation search of five other websites. Randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series studies of adolescents (girls or boys aged 10 to 19 years) eligible for World Health Organization-recommended vaccines and their parents or healthcare providers. Two review authors independently screened records, reviewed full-text articles to identify potentially eligible studies, extracted data, and assessed risk of bias, resolving discrepancies by consensus. For each included study, we calculated risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) where appropriate. We pooled study results using random-effects meta-analyses and assessed the certainty of the evidence using GRADE. We included 16 studies (eight individually randomised trials, four cluster randomised trials, three non-randomised trials, and one controlled before-after study). Twelve studies were conducted in the USA, while there was one study each from: Australia, Sweden, Tanzania, and the UK. Ten studies had unclear or high risk of bias. We categorised interventions as recipient-oriented, provider-oriented, or health systems-oriented. The interventions targeted adolescent boys or girls or both (seven studies), parents (four studies), and providers (two studies). Five studies had mixed participants that included adolescents and parents, adolescents and healthcare providers, and parents and healthcare providers. The outcomes included uptake of human papillomavirus (HPV) (11 studies); hepatitis B (three studies); and tetanus-diphtheria-acellular-pertussis (Tdap), meningococcal, HPV, and influenza (three studies) vaccines among adolescents. Health education improves HPV vaccine uptake compared to usual practice (RR 1.43, 95% CI 1.16 to 1.76; I² = 0%; 3 studies, 1054 participants; high-certainty evidence). In addition, one large study provided evidence that a complex multi-component health education intervention probably results in little to no difference in hepatitis B vaccine uptake compared to simplified information leaflets on the vaccine (RR 0.98, 95% CI 0.97 to 0.99; 17,411 participants; moderate-certainty evidence). Financial incentives may improve HPV vaccine uptake compared to usual practice (RR 1.45, 95% CI 1.05 to 1.99; 1 study, 500 participants; low-certainty evidence). However, we are uncertain whether combining health education and financial incentives has an effect on hepatitis B vaccine uptake, compared to usual practice (RR 1.38, 95% CI 0.96 to 2.00; 1 study, 104 participants; very low certainty evidence). Mandatory vaccination probably leads to a large increase in hepatitis B vaccine uptake compared to usual practice (RR 3.92, 95% CI 3.65 to 4.20; 1 study, 6462 participants; moderate-certainty evidence). Provider prompts probably make little or no difference compared to usual practice, on completion of Tdap (OR 1.28, 95% CI 0.59 to 2.80; 2 studies, 3296 participants), meningococcal (OR 1.09, 95% CI 0.67 to 1.79; 2 studies, 3219 participants), HPV (OR 0.99, 95% CI 0.55 to 1.81; 2 studies, 859 participants), and influenza (OR 0.91, 95% CI 0.61 to 1.34; 2 studies, 1439 participants) vaccination schedules (moderate-certainty evidence). Provider education with performance feedback may increase the proportion of adolescents who are offered and accept HPV vaccination by clinicians, compared to usual practice. Compared to adolescents visiting non-participating clinicians (in the usual practice group), the adolescents visiting clinicians in the intervention group were more likely to receive the first dose of HPV during preventive visits (5.7 percentage points increase) and during acute visits (0.7 percentage points for the first and 5.6 percentage points for the second doses of HPV) (227 clinicians and more than 200,000 children; low-certainty evidence). A class-based school vaccination strategy probably leads to slightly higher HPV vaccine uptake than an age-based school vaccination strategy (RR 1.09, 95% CI 1.06 to 1.13; 1 study, 5537 participants; moderate-certainty evidence). A multi-component provider intervention (including an education session, repeated contacts, individualised feedback, and incentives) probably improves uptake of HPV vaccine compared to usual practice (moderate-certainty evidence). A multi-component intervention targeting providers and parents involving social marketing and health education may improve HPV vaccine uptake compared to usual practice (RR 1.41, 95% CI 1.25 to 1.59; 1 study, 25,869 participants; low-certainty evidence). Various strategies have been evaluated to improve adolescent vaccination including health education, financial incentives, mandatory vaccination, and class-based school vaccine delivery. However, most of the evidence is of low to moderate certainty. This implies that while this research provides some indication of the likely effect of these interventions, the likelihood that the effects will be substantially different is high. Therefore, additional research is needed to further enhance adolescent immunisation strategies, especially in low- and middle-income countries where there are limited adolescent vaccination programmes. In addition, it is critical to understand the factors that influence hesitancy, acceptance, and demand for adolescent vaccination in different settings. This is the topic of an ongoing Cochrane qualitative evidence synthesis, which may help to explain why and how some interventions were more effective than others in increasing adolescent HPV vaccination coverage.

Abdullahi LH ，Kagina BM ，Ndze VN ，Hussey GD ，Wiysonge CS ... -  《Cochrane Database of Systematic Reviews》

Integrating prevention of mother-to-child HIV transmission (PMTCT) programmes with other health services for preventing HIV infection and improving HIV outcomes in developing countries.

Every year nearly 400,000 children are infected with HIV through mother-to-child transmission (MTCT), which is responsible for more than 90% of HIV infections in children. In high-income countries, the MTCT rate is less than 1% through perinatal prevention of mother-to-child HIV transmission (PMTCT) interventions. In low- and middle-income countries, PMTCT programme coverage remains low and consequently transmission rate high. The World Health Organisation recommends integration of PMTCT programmes with other healthcare services to increase access and improve uptake of these interventions. To assess the effect of integration of perinatal PMTCT measures with other health care services on coverage and service uptake compared to stand-alone PMTCT programmes and healthcare services or partially integrated PMTCT interventions. We searched the following databases, for the time period of January 1990 to August 2010: MEDLINE, EMBASE, the WHO Global Health Library, CAB abstracts, CINAHL, POPLINE, PsycINFO, Sociological Abstracts, ERIC, AEGIS, Google Scholar, New York Academy of Medicine Grey Literature, Open SIGLE, British Library Catalogue, ProQuest Dissertation & Theses Database and U.S. National Library of Medicine Gateway system. We also searched the Cochrane Database of Systematic Reviews (the Cochrane Library 2010, Issue 7), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2010, Issue 7), Database of Abstracts of Reviews on Effects (the Cochrane Library 2010, Issue 7). We also searched for ongoing trials in the WHO International Clinical Trials Registry and Controlled clinical trials (January 1990 to July 2010). We performed ISI Web of Knowledge Cited Reference Search and scanned the reference lists of the included articles for additional relevant studies. We contacted authors to locate additional eligible studies. To maximise sensitivity we did not employ any methodological filters. Randomised controlled trials (RCT), cluster-randomised controlled trials (cluster RCT), controlled clinical trials (CCT), controlled before and after (CBA) studies and interrupted time series (ITS) studies comparing integrated PMTCT interventions to non-integrated or partially integrated care for pregnant women, mothers and their infants in low- and middle-income countries. Two review authors independently ran the searches, selected studies, assessed methodological quality, and extracted data. The third review author resolved any disagreements. Only one study met the inclusion criteria. A cluster-randomised trial (12 clusters, n=7664), compared mother-infant nevirapine coverage at labour ward between intervention clinics implementing rapid HIV testing with structured nevirapine assessment and control clinics implementing informal assessment of nevirapine adherence. The authors measured nevirapine coverage in all clinics at baseline and after the implementation of the intervention. An increase of 10% (range of difference in coverage from -10% to +33%) was observed in the intervention sites compared to 10% decline in mother-infant coverage in the control sites (range of difference in coverage from -13% to 0%). The study showed that the probability of nevirapine coverage of mothers and their infants in the intervention arm compared to control arm increased from 0.89 at baseline to 1.22 during the intervention period, representing a multiplicative effect of 1.37 upon the ratio of relative risks at baseline (RR 1.37, bootstrapped 95% CI, 1.041.77). The study had a low risk of bias. No studies were found that evaluated the effectiveness of integrating other perinatal PMTCT interventions with healthcare services. We found only one study suggesting that integrating perinatal PMTCT interventions with other healthcare services in low- and middle-income countries increases the proportion of pregnant women, mothers and infants receiving PMTCT intervention. The weak evidence base does not enable making any inferences for other countries or contexts. The study that met the inclusion criteria assessed only the impact of integrating PMTCT intervention in labour ward on the proportion of mothers and their infants receiving nevirapine. The study showed significant improvement in intervention coverage but it only addressed the labour ward aspect of PMTCT programme. We did not find sufficient evidence to make definitive conclusions about the effectiveness of integration of these interventions with other health services rather than providing them as stand-alone services. Further research is urgently needed to assess the effect of integrating perinatal prevention of mother-to-child HIV transmission interventions with other health services on intervention coverage, service uptake, quality of care and health outcomes and the optimal integration modality.

Tudor Car L ，van-Velthoven MH ，Brusamento S ，Elmoniry H ，Car J ，Majeed A ，Atun R ... -  《Cochrane Database of Systematic Reviews》