Integration of the RTS,S/AS01 malaria vaccine into the Essential Programme on Immunisation in western Kenya: a qualitative longitudinal study from the health system perspective.

BACKGROUND: Malaria accounts for over half a million child deaths annually. WHO recommends RTS,S/AS01 to prevent malaria in children living in moderate-to-high malaria transmission regions. We conducted a qualitative longitudinal study to investigate the contextual and dynamic factors shaping vaccine delivery and uptake during a pilot introduction in western Kenya. METHODS: The study was conducted between Oct 3, 2019, and Mar 24, 2022. We conducted participant and non-participant observations and in-depth interviews with health-care providers, health managers, and national policymakers at three timepoints using an iterative approach and observations of practices and processes of malaria vaccine delivery. Transcripts were coded by content analysis using the consolidated framework for implementation research, to which emerging themes were added deductively and categorised into challenges and opportunities. FINDINGS: We conducted 112 in-depth interviews with 60 participants (25 health-care providers, 27 managers, and eight policy makers). Health-care providers highlighted limitations in RTS,S/AS01 integration into routine immunisation services due to the concurrent pilot evaluation and temporary adaptations for health reporting. Initial challenges related to the complexity of the four-dose schedule (up to 24-months); however, self-efficacy increased over time as the health-care providers gained experience in vaccine delivery. Low uptake of the fourth dose remained a challenge. Health managers cited insufficient trained immunisation staff and inadequate funding for supervision. Confidence in the vaccine increased among all participant groups owing to reductions in malaria frequency and severity. INTERPRETATION: Integration of RTS,S/AS01 into immunisation services in western Kenya presented substantial operational challenges most of which were overcome in the first 2 years, providing important lessons for other countries. Programme expansion is feasible with intensive staff training and retention, enhanced supervision, and defaulter-tracing to ensure uptake of all doses. FUNDING: PATH via World Health Organization; Gavi, the Vaccine Alliance; The Global Fund; and Unitaid.

Developmental and Nutritional Changes in Children with Severe Acute Malnutrition Provided with n-3 Fatty Acids Improved Ready-to-Use Therapeutic Food and Psychosocial Support: A Pilot Study in Tanzania.

Children with severe acute malnutrition (SAM) are at high risk of impaired development. Contributing causes include the inadequate intake of specific nutrients such as polyunsaturated fatty acids (PUFAs) and a lack of adequate stimulation. We conducted a pilot study assessing developmental and nutritional changes in children with SAM provided with a modified ready-to-use therapeutic food and context-specific psychosocial intervention in Mwanza, Tanzania. We recruited 82 children with SAM (6-36 months) and 88 sex- and age-matched non-malnourished children. We measured child development, using the Malawi Development Assessment Tool (MDAT), measures of family and maternal care for children, and whole-blood PUFA levels. At baseline, the mean total MDAT z-score of children with SAM was lower than non-malnourished children; -2.37 (95% confidence interval: -2.92; -1.82), as were their total n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. After 8 weeks of intervention, MDAT z-scores improved in all domains, especially fine motor, among children with SAM. Total n-3 and EPA levels increased, total n-6 fatty acids decreased, and DHA remained unchanged. Family and maternal care also improved. The suggested benefits of the combined interventions on the developmental and nutritional status of children with SAM will be tested in a future trial.

Seasonal vaccination with RTS,S/AS01E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial.

BACKGROUND: Seasonal vaccination with the RTS,S/AS01E vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years. METHODS: This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso. Children who had been enrolled in the initial 3-year trial when aged 5-17 months were initially randomly assigned individually to receive SMC with sulphadoxine-pyrimethamine and amodiaquine plus control vaccines, RTS,S/AS01E plus placebo SMC, or SMC plus RTS,S/AS01E. They continued to receive the same interventions until the age of 5 years. The primary trial endpoint was the incidence of clinical malaria over the 5-year trial period in both the modified intention-to-treat and per-protocol populations. Over the 5-year period, non-inferiority was defined as a 20% increase in clinical malaria in the RTS,S/AS01E-alone group compared with the SMC alone group. Superiority was defined as a 12% difference in the incidence of clinical malaria between the combined and single intervention groups. The study is registered with ClinicalTrials.gov, NCT04319380, and is complete. FINDINGS: In April, 2020, of 6861 children originally recruited, 5098 (94%) of the 5433 children who completed the initial 3-year follow-up were re-enrolled in the extension study. Over 5 years, the incidence of clinical malaria per 1000 person-years at risk was 313 in the SMC alone group, 320 in the RTS,S/AS01E-alone group, and 133 in the combined group. The combination of RTS,S/AS01E and SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01E (protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01E was non-inferior to SMC (hazard ratio 1·03 [95% CI 0·95 to 1·12]). The protective efficacy of the combination versus SMC over the 5-year period of the study was very similar to that seen in the first 3 years with the protective efficacy of the combination versus SMC being 57·7% (53·3 to 61·7) and versus RTS/AS01E-alone being 59·0% (54·7 to 62·8). The comparable figures for the first 3 years of the study were 62·8% (58·4 to 66·8) and 59·6% (54·7 to 64·0%), respectively. Hospital admissions for WHO-defined severe malaria were reduced by 66·8% (95% CI 40·3 to 81·5), for malarial anaemia by 65·9% (34·1 to 82·4), for blood transfusion by 68·1% (32·6 to 84·9), for all-cause deaths by 44·5% (2·8 to 68·3), for deaths excluding external causes or surgery by 41·1% (-9·2 to 68·3), and for deaths from malaria by 66·8% (-2·7 to 89·3) in the combined group compared with the SMC alone group. No safety signals were detected. INTERPRETATION: Substantial protection against malaria was sustained over 5 years by combining seasonal malaria vaccination with seasonal chemoprevention, offering a potential new approach to malaria control in areas with seasonal malaria transmission. FUNDING: UK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation). TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Acceptance of and Adherence to a Four-Dose RTS,S/AS01 Schedule: Findings from a Longitudinal Qualitative Evaluation Study for the Malaria Vaccine Implementation Programme.

BACKGROUND: The WHO recommended the use of the RTS,S/AS01 malaria vaccine (RTS,S) based on a pilot evaluation in routine use in Ghana, Kenya, and Malawi. A longitudinal qualitative study was conducted to examine facilitators and barriers to uptake of a 4-dose RTS,S schedule. METHODS: A cohort of 198 caregivers of RTS,S-eligible children from communities where RTS,S was provided through the pilot were interviewed three times over a ≈22-month, 4-dose schedule. The interviews examined caregiver perceptions and behaviors. Children's vaccination history was obtained to determine dose uptake. RESULTS: 162 caregivers remained at round 3 (R3); vaccination history was available for 152/162 children. Despite early rumors/fears, the uptake of initial doses was high, driven by vaccine trust. Fears dissipated by R2, replaced with an enthusiasm for RTS,S as caregivers perceived its safety and less frequent and severe malaria. By R3, 98/152 children had received four doses; 34 three doses; 9 one or two doses; and 11 zero doses. The health system and information barriers were important across all under-dose cases. Fears about AEFIs/safety were important in zero-, one-, and two-dose cases. Competing life/livelihood demands and complacency were found in three-dose cases. Regardless of the doses received, caregivers had positive attitudes towards RTS,S by R3. CONCLUSIONS: Findings from our study will help countries newly introducing the vaccine to anticipate and preempt reasons for delayed acceptance and missed RTS,S doses.

RTS,S/AS01 malaria vaccine pilot implementation in western Kenya: a qualitative longitudinal study to understand immunisation barriers and optimise uptake.

BACKGROUND: Malaria is a significant public health threat in sub-Saharan Africa, particularly among children. The RTS,S/AS01 malaria vaccine reduces the risk and severity of malaria in children. RTS,S/AS01 was piloted in three African countries, Ghana, Kenya and Malawi, to assess safety, feasibility and cost-effectiveness in real-world settings. A qualitative longitudinal study was conducted as part of the feasibility assessment. This analysis explores RTS,S/AS01 vaccination barriers and identifies potential motivators among caregivers in three sub-counties in western Kenya. METHODS: A cohort of 63 caregivers with a malaria vaccine eligible child was interviewed at three time points over 24 months. A sub-set of 11 caregivers whose eligible children were either partially or non-vaccinated were selected for this sub-analysis. The 5A Taxonomy for root causes of under-vaccination was used to organise the inductively-coded data into categories (awareness, acceptance, access, affordability, and activation) and identify the factors influencing uptake across caregivers. A trajectory analysis was conducted to understand changes in factors over time within each caregiver experience. Caregiver narratives are used to illustrate how the factors influencing uptake were interrelated and changed over time. RESULTS: Lack of awareness, previous negative experiences with routine childhood immunisations and the burden of getting to the health facility contributed to caregivers initially delaying uptake of the vaccine. Over time concerns about vaccine side effects diminished and anticipated vaccination benefits strongly motivated caregivers to vaccinate their children. Persistent health system barriers (e.g., healthcare provider strikes, vaccine stockouts, negative provider attitudes) meant some children missed the first-dose eligibility window by aging-out. CONCLUSIONS: Caregivers in this study believed the RTS,S/AS01 to be effective and were motivated to have their children vaccinated. Despite these positive perceptions of the malaria vaccine, uptake was substantially hindered by persistent health system constraints. Negative provider attitudes emerged as a powerful deterrent to attending immunisation services and hampered uptake of the vaccine. Strategies that focus on improving interpersonal communication skills among healthcare providers are needed.

An absence of evidence breeds contempt: A qualitative study of health system stakeholder perceptions of the quality of medicines available in Senegal.

Poor-quality medicines pose a significant challenge for health systems in low- to middle-income countries (LMICs),with recent deaths in multiple countries following ingestion of substandard cough syrups emphasising the need for quality-assurance of medicines in our increasingly interconnected global markets. Research also suggests that the source (country of manufacture) and type of medicine (generic/brand) are perceived to be associated with medicine quality. This study explores perceptions of medicines quality among national stakeholders of a medicines quality assurance system (MQAS) in sub-Saharan Africa. Through semi-structured interviews (n = 29) with managers from organisations responsible for the MQAS, public-sector doctors and nurses, and regulated private-sector pharmacists in three urban centres in Senegal in 2013. A thematic approach to analysis was undertaken with themes organised under three main categories, the source of drugs, the type of medicine, and medicines storage. A key emerging theme was the perception of the inferior quality of generic medicines, especially those produced in Asia and Africa, as they were lower in cost and thus believed to be less effective in alleviating symptoms than their brand versions. Medicines in Senegal's less regulated (informal) street markets were also thought to be of poor-quality as they were not subjected to national regulatory processes or stored appropriately, resulting in exposure to direct sunlight and high temperatures. In contrast, the interviewees expressed confidence in medicines quality within the regulated sectors (public and private retail pharmacies) attributed to stringent national medicines regulation, secure medicines supply chains and adequate technical capacity to survey and analyse for medicines quality. Also, the views expressed typically described a medicine's quality in terms of its effectiveness in alleviating the symptoms of ill health (efficacy of a medicine).These perceptions may have implications for developing national medicines policy, the procurement and supply of affordable medicines and consumers' decision-making when purchasing medicines. Indeed, a proclivity for supplying and purchasing more expensive brand medicines may act as a barrier to accessing essential medicines.

Delivery strategies for malaria vaccination in areas with seasonal malaria transmission.

BACKGROUND: Seasonal vaccination with the RTS,S/AS01E malaria vaccine given alongside seasonal malaria chemoprevention (SMC) substantially reduces malaria in young children. The WHO has recommended the use of RTS,S/AS01E, including seasonal vaccination, in areas with seasonal malaria transmission. This study aimed to identify potential strategies to deliver RTS,S/AS01E, and assess the considerations and recommendations for delivery of seasonal malaria vaccination in Mali, a country with highly seasonal malaria. METHODS: Potential delivery strategies for RTS,S/AS01E in areas with seasonal malaria were identified through a series of high level discussions with the RTS,S/AS01E plus SMC trial investigators, international and national immunisation and malaria experts, and through the development of a theory of change. These were explored through qualitative in-depth interviews with 108 participants, including national-level, regional-level and district-level malaria and immunisation programme managers, health workers, caregivers of children under 5 years of age, and community stakeholders. A national-level workshop was held to confirm the qualitative findings and work towards consensus on an appropriate strategy. RESULTS: Four delivery strategies were identified: age-based vaccination delivered via the Essential Programme on Immunisation (EPI); seasonal vaccination via EPI mass vaccination campaigns (MVCs); a combination of age-based priming vaccination doses delivered via the EPI clinics and seasonal booster doses delivered via MVCs; and a combination of age-based priming vaccination doses and seasonal booster doses, all delivered via the EPI clinics, which was the preferred strategy for delivery of RTS,S/AS01E in Mali identified during the national workshop. Participants recommended that supportive interventions, including communications and mobilisation, would be needed for this strategy to achieve required coverage. CONCLUSIONS: Four delivery strategies were identified for administration of RTS,S/AS01E alongside SMC in countries with seasonal malaria transmission. Components of these delivery strategies were defined as the vaccination schedule, and the delivery system(s) plus the supportive interventions needed for the strategies to be effective. Further implementation research and evaluation is needed to explore how, where, when and what effective coverage is achievable via these new strategies and their supportive interventions.

SD-Bioline malaria rapid diagnostic test performance and time to become negative after treatment of malaria infection in Southwest Nigerian Children.

Context and Aim: Given the challenges of microscopy, we compared its performance with SD-Bioline malaria rapid diagnostic test (MRDT) and polymerase chain reaction (PCR) and evaluated the time it took for positive results to become negative after treatment of children with acute uncomplicated malaria. Subjects and Methods: We present the report of 485 participants with complete MRDT, microscopy, and PCR data out of 511 febrile children aged 3-59 months who participated in a cohort study over a 12-month period in rural and urban areas of Ibadan, Nigeria. MRDT-positive children received antimalaria and tested at every visit over 28 days. Speciation was also carried out by PCR. Results: With microscopy as the gold standard, SD-Bioline™ had 95.2% sensitivity, 66.4% specificity, 67.5% positive predictive value (PPV), and 94.9 negative predictive value (NPV), while with PCR the findings were 84.3% sensitivity, 66.5% specificity, 72.7% PPV, and 80.1% NPV. PCR speciation of malaria parasites revealed 91.6% Plasmodium falciparum, 18.9% Plasmodium malariae, and 4.4% Plasmodium ovale. Among the 47 children with P. malariae infections, 66.0% were coinfected with P. falciparum, while 54.6% cases of P. ovale occurred as coinfections with P. falciparum. The median time to a negative MRDT was 23.2 days, while the median time to a negative malaria microscopy was 3.8 days. The two survival curves were significantly different. Conclusions: The SD-BiolineTM MRDT performed well, with remarkable persistence of rapid test-positive for an average of 23 days post treatment. The prevalence of P. malaria is somewhat greater than expected.

Résumé Contexte et objectif: Compte tenu des défis de la microscopie, nous avons comparé le test de diagnostic rapide du paludisme SD-Bioline (MRDT) avec la réaction en chaîne par polymérase (PCR) et évalué le temps qu'il a fallu pour que des résultats positifs deviennent négatifs après le traitement d'enfants atteints de paludisme aigu non compliqué. Sujets et méthodes: Nous présentons le rapport de 485 participants avec des données complètes de MRDT, de microscopie et de PCR sur 511 enfants fébriles âgés de 3 à 59 mois qui ont participé à une étude de cohorte sur une période de 12 mois dans les zones rurales et urbaines d'Ibadan, Nigeria. Les enfants positifs au MRDT ont reçu un antipaludique et ont été testés à chaque visite pendant 28 jours. La spéciation a également été réalisée par PCR. Résultats: Avec la microscopie comme référence, SD-Bioline TM avait une sensibilité de 95,2 %, une spécificité de 66,4 %, une valeur prédictive positive (VPP) de 67,5 % et une valeur prédictive négative (VPN) de 94,9 %, tandis qu'avec la PCR, les résultats étaient de 84,3 % de sensibilité, 66,5 % de spécificité, 72,7 % de VPP et 80,1 % de VPN. La spéciation par PCR des parasites du paludisme a révélé 91,6 % de Plasmodium falciparum, 18,9 % de Plasmodium malariae et 4,4 % de Plasmodium ovale. Parmi les 47 enfants atteints d'infections à P. malariae, 66,0 % étaient co-infectés par P. falciparum, tandis que 54,6 % des cas de P. ovale se sont produits sous forme de co-infections par P. falciparum. Le délai médian jusqu'à un MRDT négatif était de 23,2 jours, tandis que le délai médian jusqu'à une microscopie négative du paludisme était de 3,8 jours. Les deux courbes de survie étaient significativement différentes. Conclusions: Le SD-BiolineTM MRDT a donné de bons résultats, avec une infection à P. malariae un peu plus élevée que attendu dans la population et persistance remarquable des résultats positifs aux tests de diagnostic rapide pendant une moyenne de plus de 23. Mots-clés: Paludisme, microscopie, Nigéria, réaction en chaîne par polymérase, test de diagnostic rapide, spéciationjours après le traitement.

SD bioline malaria rapid diagnostic test performance and time to become negative after treatment of malaria infection in southwest Nigerian children

Context and Aim: Given the challenges of microscopy, we compared its performance with SD Bioline malaria rapid diagnostic test (MRDT) and polymerase chain reaction (PCR) and evaluated the time it took for positive results to become negative after treatment of children with acute uncomplicated malaria. Subjects and Methods: We present the report of 485 participants with complete MRDT, microscopy, and PCR data out of 511 febrile children aged 3­59 months who participated in a cohort study over a 12 month period in rural and urban areas of Ibadan, Nigeria. MRDT positive children received antimalaria and tested at every visit over 28 days. Speciation was also carried out by PCR. Results: With microscopy as the gold standard, SD-Bioline™ had 95.2% sensitivity, 66.4% specificity, 67.5% positive predictive value (PPV), and 94.9 negative predictive value (NPV), while with PCR the findings were 84.3% sensitivity, 66.5% specificity, 72.7% PPV, and 80.1% NPV. PCR speciation of malaria parasites revealed 91.6% Plasmodium falciparum, 18.9% Plasmodium malariae, and 4.4% Plasmodium ovale. Among the 47 children with P. malariae infections, 66.0% were coinfected with P. falciparum, while 54.6% cases of P. ovale occurred as coinfections with P. falciparum. The median time to a negative MRDT was 23.2 days, while the median time to a negative malaria microscopy was 3.8 days. The two survival curves were significantly different. Conclusions: The SD BiolineTM MRDT performed well, with remarkable persistence of rapid test-positive for an average of 23 days post treatment. The prevalence of P. malaria is somewhat greater than expected.

Non-Malaria Causes of Fever among under-5 Children with Negative Results for Malaria Rapid Diagnostic Test in South-Western Nigeria.

BACKGROUND: Although the global malaria burden is decreasing, there are still concerns about overdiagnosis of malaria and the danger of misdiagnosis of non-malaria causes of fever. Clinicians continue to face the challenge of differentiating between these causes despite the introduction of malaria rapid diagnostic tests (mRDTs). AIM: To determine the prevalence and causes of non-malaria-caused fever in children in South-Western Nigeria. METHODS: Secondary analysis of data obtained to evaluate the effect of restricting antimalarial treatment to positive mRDT children in rural and urban areas of southwest Nigeria. Clinical examinations, laboratory tests for malaria parasites (including thick blood film and mRDT) and bacterial identification were performed on children aged 3-59 months (n = 511). The non-malaria group comprised febrile children who had both negative mRDT and microscopy results, while the malaria group included those who were positive for either mRDT or microscopy. We compared the causes of fever among children with non-malaria fever and those with malaria. RESULTS: The prevalence of non-malaria fever and bacteria-malaria co-infection was 37.2% and 2.0%, respectively. Non-malarial pathogens identified were viral (54.7%) and bacterial (32.1%) infections. The bacterial infections included bacteriaemia (2.7%), urinary tract infections (21.6%), skin infections (11.6%) and otitis media (2.6%). The leading bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae. CONCLUSION: The high prevalence and wide range of non-malarial infections reinforces the need for point-of-care tests to identify bacterial and viral infections to optimize the treatment of febrile illnesses in malaria-endemic areas.

Perceptions of quality and the integrated delivery of family planning with childhood immunisation services in Kenya and Uganda.

The integration of family planning (FP) with childhood immunisations is considered a promising approach to addressing postpartum women's unmet need for FP in resource limited settings. This study set out to examine client and health provider perceptions of the quality of FP services that were integrated with childhood immunisations in Kenya and Uganda. Semi-structured interviews with clients (n = 30) and health providers (n = 27) were conducted in 16 rural health facilities. Interviews centred on the respondents' experiences receiving/delivering FP services, their interactions with providers/clients, and their views on the quality of FP services. Client and provider perceptions of quality were compared through a thematic analysis of interview transcripts, and findings were synthesised using Jain and Hardee's revised FP Quality of Care Framework. Using audit data, health facility characteristics and resources were also summarised through descriptive statistics to contextualise the qualitative findings. The dignity and respect experienced by clients was central to the respondents' perceptions of quality. These two dimensions were not conceptualised as distinct facets of quality, but were instead perceived to be a product of the 1) access to needed services, 2) choice of contraceptives, 3) interpersonal communication, 4) information, and 5) confidentiality afforded to clients. Additionally, clients and providers alike believed that the integration of FP services with childhood immunisations had a positive effect on clients' access to needed services and on the confidentiality they experienced in a context where modern contraceptive use was stigmatised and where a lack of support from some husbands impeded access to FP services. Understanding clients' and providers' conceptualisation of quality is critical to the design of high quality and client-centred integrated FP services.

Using donor funding to catalyse investment in malaria prevention in Ghana: an analysis of the potential impact on public and private sector expenditure.

BACKGROUND: An estimated 1.5 billion malaria cases and 7.6 million malaria deaths have been averted globally since 2000; long-lasting insecticidal nets (LLINs) have contributed an estimated 68% of this reduction. Insufficient funding at the international and domestic levels poses a significant threat to future progress and there is growing emphasis on the need for enhanced domestic resource mobilization. The Private Sector Malaria Prevention (PSMP) project was a 3-year intervention to catalyse private sector investment in malaria prevention in Ghana. METHODS: To assess value for money of the intervention, non-donor expenditure in the 5 years post-project catalysed by the initial donor investment was predicted. Non-donor expenditure catalysed by this investment included: workplace partner costs of malaria prevention activities; household costs in purchasing LLINs from retail outlets; domestic resource mobilization (public sector financing and private investors). Annual ratios of projected non-donor expenditure to annualized donor costs were calculated for the 5 years post-project. Alternative scenarios were constructed to explore uncertainty around future consequences of the intervention. RESULTS: The total donor financial cost of the 3-year PSMP project was USD 4,418,996. The average annual economic donor cost per LLIN distributed through retail sector and workplace partners was USD 21.17 and USD 7.55, respectively. Taking a 5-year post-project time horizon, the annualized donor investment costs were USD 735,805. In the best-case scenario, each USD of annualized donor investment led to USD 4.82 in annual projected non-donor expenditure by the fifth-year post-project. With increasingly conservative assumptions around the project consequences, this ratio decreased to 3.58, 2.16, 1.07 and 0.93 in the "very good", "good", "poor" and "worst" case scenarios, respectively. This suggests that in all but the worst-case scenario, donor investment would be exceeded by the non-donor expenditure it catalysed. CONCLUSIONS: The unit cost per net delivered was high, reflecting considerable initial investment costs and relatively low volumes of LLINs sold during the short duration of the project. However, taking a longer time horizon and broader perspective on the consequences of this complex catalytic intervention suggests that considerable domestic resources for malaria control could be mobilized, exceeding the value of the initial donor investment.

Integrated delivery of family planning and childhood immunization services: a qualitative study of factors influencing service responsiveness in Malawi.

Evidence from several countries in sub-Saharan Africa suggests that the integration of family planning (FP) with childhood immunization services can help reduce the unmet need for FP among postpartum women without undermining the uptake of immunizations. However, the quality and responsiveness of FP services that are integrated with childhood immunizations remain understudied. A qualitative study was conducted in two districts of Malawi, which examined the factors influencing the responsiveness of FP services that were integrated with childhood immunizations in monthly public outreach clinics. Semi-structured interviews with clients (n = 23) and FP providers (n = 10) and a clinic audit were carried out in six clinics. Hardware (material) and software (relational) factors influencing service responsiveness were identified through thematic and framework analyses of interview transcripts, and clinic characteristics were summarized from the audit data to contextualize the qualitative findings. Overall, 13 factors were found to influence service responsiveness in terms of the ease of access, choice of provider, environment, service continuity, confidentiality, communication, dignity and FP counselling afforded to clients. Among these factors, hardware deficiencies, including the absence of a dedicated building for the provision of FP services and the lack of FP commodities in clinics, were perceived to negatively affect service responsiveness. Crucially, the providers' use of their agency to alter the delivery of services was found to mitigate the negative effects of some hardware deficits on the ease of access, choice of provider, environment and confidentiality experienced by clients. This study contributes to an emerging recognition that providers can offset the effect of hardware deficiencies when services are integrated if they are afforded sufficient flexibility to make independent decisions. Consideration of software elements in the design and delivery of FP services that are integrated with childhood immunizations is therefore critical to optimize the responsiveness of these services.

"It was my own decision": the transformational shift that influences a woman's decision to use contraceptives covertly.

BACKGROUND: Family planning (FP) is an important element of sexual and reproductive health and rights, but socio-cultural barriers and unbalanced gender relations often limit women's decision-making about contraceptive use. Covert contraceptive use (CCU) exemplifies the limits on women's decision-making and represents a way in which some women overcome constraints to achieve their reproductive goals. This study explores the decision-making process through which women choose to use contraceptives covertly. METHODS: A qualitative synthesis was conducted using data from women, health providers, community members, health administrators, and intervention implementers (n = 400) to explore the decision-making process through which women choose to use contraceptives covertly. Interviews and focus group discussions were conducted at two time points as part of an evaluation of interventions integrating FP and childhood immunisation services at sites in Benin, Kenya, Malawi and Uganda. The sexual and reproductive health empowerment framework by Karp et al. (2020) was adapted and used to guide the analysis. RESULTS: Women recognised that although they suffered the negative consequences of frequent pregnancies and of raising large families, they lacked overt decision-making power over their fertility. Women were confident to engage in CCU because they believed their husbands did not understand these consequences nor acknowledged their suffering, which justified not informing them. CCU was a difficult choice however, women felt comfortable voicing their reproductive preferences in settings where health providers were supportive. CONCLUSIONS: Women chose to use contraceptives covertly when they questioned the unfairness of their situation and recognised their own power to act in accordance with their reproductive preferences. This represented an important shift in a woman's perception of who is entitled to make decisions about contraceptive use. Importantly, health providers can play a key role in supporting women's autonomous decision making about contraceptive use and should be careful not to undermine women's confidence.

Challenges and lessons learned during the planning and early implementation of the RTS,S/AS01E malaria vaccine in three regions of Ghana: a qualitative study.

BACKGROUND: In 2019, the RTS,S/AS01E malaria vaccine was introduced on a pilot basis in six regions of Ghana by the Ministry of Health/Ghana Health Service as part of the WHO-coordinated Malaria Vaccine Implementation Programme (MVIP). This is the first time a malaria vaccination programme has been implemented in any country. This paper describes the challenges faced, and lessons learned, during the planning and early implementation of the RTS,S/AS01E vaccine in three out of the six regions that implemented the programme in Ghana. METHODS: Twenty-one in-depth interviews were conducted with regional and district health service managers and frontline health workers three months after the start of MVIP in May 2019. Data were coded using NVivo software version 12 and a coding framework was developed to support thematic analysis to identify the challenges and lessons learned during the RTS,S/AS01E implementation pilot, which were also categorized into the Consolidated Framework for Implementation Research (CFIR). RESULTS: Participants reported challenges related to the characteristics of the intervention, such as issues with the vaccine schedule and eligibility criteria, and challenges related to how it was implemented as a pilot programme. Additionally, major challenges were faced due to the spread of rumours leading to vaccine refusals; thus, the outer setting of the CFIR was adapted to accommodate rumours within the community context. Health service managers and frontline health workers also experienced challenges with the process of implementing RTS,S/AS01E, including inadequate sensitization and training, as well as issues with the timeline. They also experienced challenges associated with the features of the systems within which the vaccine was being implemented, including inadequate resources for cold-chain at the health facility level and transportation at the district and health facility levels. This study identified the need for a longer, more intensive and sustained delivery of contextually-appropriate sensitization prior to implementation of a programme such as MVIP. CONCLUSIONS: This study identified 12 main challenges and lessons learned by health service managers and health workers during the planning and early implementation phases of the RTS,S/AS01E pilot introduction in Ghana. These findings are highly relevant to the likely scale-up of RTS,S/AS01E within Ghana and possible implementation in other African countries, as well as to other future introductions of novel vaccines.

Integrated delivery of family planning and childhood immunisation services: a mixed methods assessment of service responsiveness.

BACKGROUND: Postpartum women represent a considerable share of the global unmet need for modern contraceptives. Evidence suggests that the integration of family planning (FP) with childhood immunisation services could help reduce this unmet need by providing repeat opportunities for timely contact with FP services. However, little is known about the clients' experiences of FP services that are integrated with childhood immunisations, despite being crucial to contraceptive uptake and repeat service utilisation. METHODS: The responsiveness of FP services that were integrated with childhood immunisations in Malawi was assessed using cross-sectional convergent mixed methods. Exit interviews with clients (n=146) and audits (n=15) were conducted in routine outreach clinics. Responsiveness scores across eight domains were determined according to the proportion of clients who rated each domain positively. Text summary analyses of qualitative data from cognitive interviewing probes were also conducted to explain responsiveness scores. Additionally, Spearman rank correlation and Pearson's chi-squared test were used to identify correlations between domain ratings and to examine associations between domain ratings and client, service and clinic characteristics. RESULTS: Responsiveness scores varied across domains: dignity (97.9%); service continuity (90.9%); communication (88.7%); ease of access (77.2%); counselling (66.4%); confidentiality (62.0%); environment (53.9%) and choice of provider (28.4%). Despite some low performing domains, 98.6% of clients said they would recommend the clinic to a friend or family member interested in FP. The choice of provider, communication, confidentiality and counselling ratings were positively associated with clients' exclusive use of one clinic for FP services. Also, the organisation of services in the clinics and the providers' individual behaviours were found to be critical to service responsiveness. CONCLUSIONS: This study establishes that in routine outreach clinics, FP services can be responsive when integrated with childhood immunisations, particularly in terms of the dignity and service continuity afforded to clients, though less so in terms of the choice of provider, environment, and confidentiality experienced. Additionally, it demonstrates the value of combining cognitive interviewing techniques with Likert questions to assess service responsiveness.

Acceptability of family planning in a changing context in Uganda: a realist evaluation at two time points.

OBJECTIVES: This study sought to understand, during an intervention which integrated family planning (FP) and immunisation, (1) if and how prevailing contextual factors influenced acceptability and use of modern contraceptive methods (MCMs) in a pastoral community in Uganda, (2) what mechanisms were triggered by these contextual factors (3) if these contextual factors changed between two time points 2 years apart and (4) the impact of contextual changes on mechanisms triggered and acceptability and use outcomes. DESIGN: Qualitative realist evaluation over two time points. SETTING: Government health facilities in Moroto District, Karamoja, Uganda. PARTICIPANTS: 69 participants involved in the delivery and uptake of integrated FP and childhood immunisation services. INTERVENTION: Integrated delivery of FP and childhood immunisation services offered to women accessing immunisation services in health facilities between January 2016 and December 2019. RESULTS: Four key themes were identified that encompassed context and mechanisms influencing acceptability of MCMs across both time points of the evaluation. These were: (1) fear of side effects of MCMs; (2) preference for natural FP methods; (3) pastoral lifestyles in the community and (4) food insecurity. The context of these themes changed over time leading to the triggering of mechanisms with an overall increase in acceptability of MCMs over time. Key mechanisms of acceptability triggered included: affective attitude, intervention coherence, self-efficacy, perceived effectiveness and opportunity cost, leading to the development of three context-acceptability theories. CONCLUSIONS: In this study, social and cultural norms played a strong role in influencing acceptability of the intervention. The context combined with intervention components were found to trigger several mechanisms that mapped to constructs of diffusion of innovations and acted as catalysts for mechanisms of acceptability. The context in which the intervention was implemented changed leading to the triggering of mechanisms and an increase in the perceived value and acceptability of MCM use.

Co-circulation of Chikungunya Virus during the 2015-2017 Zika Virus Outbreak in Pernambuco, Brazil: An Analysis of the Microcephaly Epidemic Research Group Pregnancy Cohort.

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

Towards universal health coverage for people with stroke in South Africa: a scoping review.

OBJECTIVES: To explore the opportunities and challenges within the health system to facilitate the achievement of universal health coverage (UHC) for people with stroke (PWS) in South Africa (SA). SETTING: SA. DESIGN: Scoping review. SEARCH METHODS: We conducted a scoping review of opportunities and challenges to achieve UHC for PWS in SA. Global and Africa-specific databases and grey literature were searched in July 2020. We included studies of all designs that described the healthcare system for PWS. Two frameworks, the Health Systems Dynamics Framework and WHO Framework, were used to map data on governance and regulation, resources, service delivery, context, reorientation of care and community engagement. A narrative approach was used to synthesise results. RESULTS: Fifty-nine articles were included in the review. Over half (n=31, 52.5%) were conducted in Western Cape province and most (n=41, 69.4%) were conducted in urban areas. Studies evaluated a diverse range of health system categories and various outcomes. The most common reported component was service delivery (n=46, 77.9%), and only four studies (6.7%) evaluated governance and regulation. Service delivery factors for stroke care were frequently reported as poor and compounded by context-related limiting factors. Governance and regulations for stroke care in terms of government support, investment in policy, treatment guidelines, resource distribution and commitment to evidence-based solutions were limited. Promising supporting factors included adequately equipped and staffed urban tertiary facilities, the emergence of Stroke units, prompt assessment by health professionals, positive staff attitudes and care, two clinical care guidelines and educational and information resources being available. CONCLUSION: This review fills a gap in the literature by providing the range of opportunities and challenges to achieve health for all PWS in SA. It highlights some health system areas that show encouraging trends to improve service delivery including comprehensiveness, quality and perceptions of care.

Healthcare provider and pregnant women's perspectives on the implementation of intermittent screening and treatment with dihydroartemisinin-piperaquine for malaria in pregnancy in western Kenya: a qualitative study.

BACKGROUND: In malaria endemic regions in Kenya, pregnant women are offered long-lasting insecticidal nets and intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) at antenatal care (ANC) to prevent the adverse effects of malaria. Fears of growing SP resistance have heightened the search for alternative strategies. The implementation feasibility of intermittent screening and treatment (ISTp) with dihydroartemisinin-piperaquine (DP) in routine ANC settings was evaluated using qualitative and quantitative methods, including the exploration of healthcare provider and pregnant women's perceptions. METHODS: Qualitative methods included data from 13 focus group discussions (FGDs) with pregnant women and 43 in-depth interviews with healthcare providers delivering ANC services. FGDs were conducted with women who had received either ISTp-DP or current policy (IPTp-SP). Thematic analysis was used to explore experiences among women and providers and findings were used to provide insights into results of the parallel quantitative study. RESULTS: Women were accepting of testing with rapid diagnostic tests (RDTs) and receiving treatment if malaria positive. Providers perceived DP to be an effective drug and well tolerated by women. Some providers indicated a preference for test and treat strategies to reduce unnecessary exposure to medication in pregnancy, others preferred a hybrid strategy combining screening at every ANC visit followed by IPTp-SP for women who tested negative, due to the perception that RDTs missed some infections and concerns about the growing resistance to SP. Testing with RDTs during ANC was appreciated as it was perceived to reduce wait times. The positive attitude of healthcare providers towards ISTp supports findings from the quantitative study that showed a high proportion (90%) of women were tested at ANC. There were concerns about affordability of DP and the availability of sufficient RDT stocks. CONCLUSION: In ANC settings, healthcare providers and pregnant women found ISTp-DP to be an acceptable strategy for preventing malaria in pregnancy when compared with IPTp-SP. DP was considered an effective anti-malarial and a suitable alternative to IPTp-SP in the context of SP resistance. Despite providers' lack of confidence in RDT results at current levels of sensitivity and specificity, the quantitative findings show their willingness to test women routinely at ANC.