Lessons learnt from human papillomavirus (HPV) vaccination in 45 low- and middle-income countries.

OBJECTIVE: To synthesise lessons learnt and determinants of success from human papillomavirus (HPV) vaccine demonstration projects and national programmes in low- and middle-income countries (LAMICs). METHODS: Interviews were conducted with 56 key informants. A systematic literature review identified 2936 abstracts from five databases; after screening 61 full texts were included. Unpublished literature, including evaluation reports, was solicited from country representatives; 188 documents were received. A data extraction tool and interview topic guide outlining key areas of inquiry were informed by World Health Organization guidelines for new vaccine introduction. Results were synthesised thematically. RESULTS: Data were analysed from 12 national programmes and 66 demonstration projects in 46 countries. Among demonstration projects, 30 were supported by the GARDASIL® Access Program, 20 by Gavi, four by PATH and 12 by other means. School-based vaccine delivery supplemented with health facility-based delivery for out-of-school girls attained high coverage. There were limited data on facility-only strategies and little evaluation of strategies to reach out-of-school girls. Early engagement of teachers as partners in social mobilisation, consent, vaccination day coordination, follow-up of non-completers and adverse events was considered invaluable. Micro-planning using school/ facility registers most effectively enumerated target populations; other estimates proved inaccurate, leading to vaccine under- or over-estimation. Refresher training on adverse events and safe injection procedures was usually necessary. CONCLUSION: Considerable experience in HPV vaccine delivery in LAMICs is available. Lessons are generally consistent across countries and dissemination of these could improve HPV vaccine introduction

Do community-based active case-finding interventions have indirect impacts on wider TB case detection and determinants of subsequent TB testing behaviour? A systematic review

Funding: This work was made possible through grants provided by the WHO Global TB Programme. RMB, ELC, and PM hold Wellcome fellowships: 203905/Z/16/Z (RMB), 200901/Z/16/Z (ELC), and 206575/Z/17/Z (PM). MR, LT, and HA are funded by part of the European and Developing Countries Clinical Trials Partnership 2 programme supported by the EU (grant number RIA2016S-1632-TREATS). AES is supported by a National Institutes of Health (NIH) grant K23AI140918. WHO facilitated discussions among authors at the design stage and contributed to this manuscript but had no role in the conduct or writing of the WHO review.Community-based active case-finding (ACF) may have important impacts on routine TB case-detection and subsequent patient-initiated diagnosis pathways, contributing “indirectly” to infectious diseases prevention and care. We investigated the impact of ACF beyond directly diagnosed patients for TB, using routine case-notification rate (CNR) ratios as a measure of indirect effect. We systematically searched for publications 01-Jan-1980 to 13-Apr-2020 reporting on community-based ACF interventions compared to a comparison group, together with review of linked manuscripts reporting knowledge, attitudes, and practices (KAP) outcomes or qualitative data on TB testing behaviour. We calculated CNR ratios of routine case-notifications (i.e. excluding cases identified directly through ACF) and compared proxy behavioural outcomes for both ACF and comparator communities. Full text manuscripts from 988 of 23,883 abstracts were screened for inclusion; 36 were eligible. Of these, 12 reported routine notification rates separately from ACF intervention-attributed rates, and one reported any proxy behavioural outcomes. Two further studies were identified from screening 1121 abstracts for linked KAP/qualitative manuscripts. 8/12 case-notification studies were considered at critical or serious risk of bias. 8/11 non-randomised studies reported bacteriologically-confirmed CNR ratios between 0.47 (95% CI:0.41–0.53) and 0.96 (95% CI:0.94–0.97), with 7/11 reporting all-form CNR ratios between 0.96 (95% CI:0.88–1.05) and 1.09 (95% CI:1.02–1.16). One high-quality randomised-controlled trial reported a ratio of 1.14 (95% CI 0.91–1.43). KAP/qualitative manuscripts provided insufficient evidence to establish the impact of ACF on subsequent TB testing behaviour. ACF interventions with routine CNR ratios >1 suggest an indirect effect on wider TB case-detection, potentially due to impact on subsequent TB testing behaviour through follow-up after a negative ACF test or increased TB knowledge. However, data on this type of impact are rarely collected. Evaluation of routine case-notification, testing and proxy behavioural outcomes in intervention and comparator communities should be included as standard methodology in future ACF campaign study designs.Peer reviewe

Tuberculosis diagnosis cascade in Blantyre, Malawi : a prospective cohort study

Wellcome Trust. PM is funded by Wellcome (206575/Z/17/Z). ELC is funded by Wellcome (200901/Z/16/Z). ELW received salary funding from the UK Medical Research Council (grant number MR/K012126/1), this award is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union.Background Tuberculosis (TB) control relies on early diagnosis and treatment. International guidelines recommend systematic TB screening at health facilities, but implementation is challenging. We investigated completion of recommended TB screening steps in Blantyre, Malawi. Methods A prospective cohort recruited adult outpatients attending Bangwe primary clinic. Entry interviews were linked to exit interviews. The proportion of participants progressing through each step of the diagnostic pathway were estimated. Factors associated with request for sputum were investigated using multivariable logistic regression. Results Of 5442 clinic attendances 2397 (44%) had exit interviews. In clinically indicated participants (n = 445) 256 (57.5%) were asked about cough, 36 (8.1%) were asked for sputum, 21 (4.7%) gave sputum and 1 (0.2%) received same-day results. Significant associations with request for sputum were: any TB symptom (aOR:3.20, 95%CI:2.02–5.06), increasing age (aOR:1.02, 95%CI:1.01–1.04 per year) and for HIV-negative participants only, a history of previous TB (aOR:3.37, 95%CI:1.45–7.81). Numbers requiring sputum tests (26/day) outnumbered diagnostic capacity (8–12/day). Conclusions Patients were lost at every stage of the TB care cascade, with same day sputum submission following all steps of the diagnosis cascade achieved in only 4.7% if clinically indicated. Infection control strategies should be implemented, with reporting on early steps of the TB care cascade formalised. High-throughput screening interventions, such as digital CXR, that can achieve same-day TB diagnosis are urgently needed to meet WHO End TB goals.Peer reviewe

New pneumococcal conjugate vaccine introductions in four sub-Saharan African countries: a cross-country analysis of health systems\u2019 impacts

Background: Pneumonia is a main cause of under-five mortality in low-income settings. The pneumococcal conjugate vaccine (PCV) has been introduced in many countries as a tool in the disease\u2019s prevention. Although PCV\u2019s effectiveness has been established, less is known about the effects of introducing additional injectable vaccines into routine immunisation programmes, particularly in the context of resource-constrained settings. Objectives: To explore the effects of PCV introduction on the immunisation programmes and health systems in four low-income countries. Methods: This study was carried out in Cameroon, Ethiopia, Kenya and Mali. Three to four regions and nine to 10 districts were selected within each country. Semi-structured interviews were carried out at national, regional and district levels (n=173). Researcher-administered questionnaires were completed with facility staff (n=124). Routine data on monthly vaccination activities were collected at district and facility levels. Results: PCV was generally well integrated into existing routine immunisation. Little or no impact was found in most areas of the health systems. Some minor effects were found on immunisation programmes, particularly in areas with either planning activities or investments e.g. staff skills were strengthened and there were limited improvements in surveillance. Although health sector workers perceived increases in the coverage of other vaccines following the introduction of PCV, routine service data did not confirm this claim. No substantial impacts were seen in health system management, service delivery or performance. Conclusions: The introduction of PCV had marginal impacts on the Expanded Programme for Immunisation and little to none on broader health systems

Prevalence of bacteriologically-confirmed pulmonary tuberculosis in urban Blantyre, Malawi 2019-20: substantial decline compared to 2013-14 national survey

Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 115 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters. Consenting eligible participants (household residents ≥ 18 years) were interviewed, including for cough (any duration), and offered HIV testing and chest X-ray; participants with cough and/or abnormal X-ray provided two sputum samples for microscopy, Xpert MTB/Rif and mycobacterial culture. TB disease prevalence and risk factors for prevalent TB were calculated using complete-case analysis, multiple imputation, and inverse probability weighting. Of 20,899 eligible adults, 15,897 (76%) were interviewed, 13,490/15,897 (85%) had X-ray, and 1,120/1,394 (80%) sputum-eligible participants produced at least one specimen, giving 15,318 complete cases (5,895, 38% men). 29/15,318 had bacteriologically-confirmed TB (189 per 100,000 complete-case (cc) / 150 per 100,000 with inverse weighting (iw)). Men had higher burden (cc: 305 [95% CI:144–645] per 100,000) than women (cc: 117 [95% CI:65–211] per 100,000): cc adjusted odds ratio (aOR) 2.70 (1.26–5.78). Other significant risk factors for prevalent TB on complete-case analysis were working age (25–49 years) and previous TB treatment, but not HIV status. Multivariable analysis of imputed data was limited by small numbers, but previous TB and age group 25–49 years remained significantly associated with higher TB prevalence. Pulmonary TB prevalence for Blantyre was considerably lower than the 1,014 per 100,000 for urban Malawi in the 2013–14 national survey, at 150–189 per 100,000 adults, but some groups, notably men, remain disproportionately affected. TB case-finding is still needed for TB elimination in Blantyre, and similar urban centres, but should focus on reaching the highest risk groups, such as older men

When can research from one setting be useful in another? Understanding perceptions of the applicability and transferability of research.

Determining whether research findings from one setting are relevant to another is complex and poorly understood. This study aimed to explore the factors affecting whether research from other settings was perceived to be of potential use to those working in or researching maternal health in Ghana. Semi-structured interviews were conducted with 69 purposively sampled government decision-makers, researchers and other stakeholders working in maternal health in Ghana in 2008-09. The most influential factors affecting perceptions of applicability/transferability were the study's congruence with interviewees' previous experiences and beliefs. Interventions' adaptability was also considered crucial (and more important than remaining faithful to the original intervention). However, it was frequently considered a distinct stage in the research use process rather than a consideration of applicability/transferability. More attention was paid to the implementability of the intervention in the new setting, than to whether it would be as effective there. Interpretations of intervention descriptions and evaluation findings varied between interviewees, even when the same information was presented. This study is one of the first to explore perceptions of applicability/transferability of public health research among researchers and potential research users in a low-income setting. The findings suggest that existing frameworks of applicability/transferability do not reflect the factors considered to be most important in Ghana

Collection tools for: "Assessing the capacity of primary health care facilities in Nigeria to deliver eye health promotion: Results of a mixed-methods feasibility study"

Collection tools produced as part of a mixed-methods feasibility study to assess the capacity of primary health care facilities in Nigeria to deliver eye health promotion. It contains a JCHEW data form and checklist, JCHEW questionnaire, VHW questionnaire, criteria for selection of facilities for semi structured interviews and topic guide for facility heads and district level supervisors

Can cash transfer interventions increase contraceptive use and reduce adolescent birth and pregnancy in low and middle income countries? A systematic review and meta-analysis.

Becoming pregnant and giving birth under the age of 20 is associated with a range of adverse social, socioeconomic and health outcomes for adolescent girls and their children in Low and middle income countries. Cash transfers are an example of a structural intervention that can change the local social and economic environment, and have been linked with positive health and social outcomes across several domains. As part of a wider review of structural adolescent contraception interventions, we conducted a systematic review on the impact of cash transfers on adolescent contraception and fertility. Fifteen studies were included in the review with eleven studies providing evidence for meta-analyses on contraception use, pregnancy and childbearing. The evidence suggests that cash transfer interventions are generally ineffective in raising levels of contraceptive use. However, cash transfer interventions did reduce levels of early pregnancy (OR 0.90, 95% CI 0.81 to 1.00). There was suggestive evidence that conditional, but not unconditional, cash transfers reduce levels of early childbearing. Given that much of the evidence is drawn from interventions providing cash transfers conditional on school attendance, supporting school attendance may enable adolescent girls and young women to make life choices that do not involve early pregnancy

What works for human papillomavirus vaccine introduction in low and middle-income countries?

Since 2007, low and middle-income countries (LMICs) have gained experience delivering HPV vaccines through HPV vaccination pilots, demonstration projects and national programmes. This commentary summarises lessons from HPV vaccination experiences in 45 LMICs and what works for HPV vaccination introduction. Methods included a systematic literature review, unpublished document review, and key informant interviews. Data were extracted from 61 peer-reviewed articles, 11 conference abstracts, 188 technical reports, and 56 interviews, with quantitative data analysed descriptively and qualitative data analysed thematically. Key lessons are described under five themes of preparation, communications, delivery, coverage achievements, and sustainability. Lessons learnt were generally consistent across countries and projects and sufficient lessons have been learnt for countries to deliver HPV vaccine through phased national rollout rather than demonstration projects. However, challenges remain in securing the political will and financial resources necessary to implement successful national programmes. Keywords: Cervical cancer prevention, Human papillomavirus, Vaccination, Low and middle-income countries, Demonstration project