PATH

Background While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. Methods This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. Results This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey–derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. Conclusion ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.

Background Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria. Methods This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose–response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia’s interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding. Results The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75–0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66–0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population. Conclusions CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.

Objectives: In Vietnam, although surveillance and control of multidrug-resistant organisms is a national priority, information on the burden of these pathogens remains scarce. At the University Medical Center in Ho Chi Minh City, we assessed the proportion of carbapanemase-producing carbapenem-resistant organisms (CP-CRO) and evaluated an intervention package to prevent transmission of carbapenemase-producing carbapenem-resistant Enterobacterieacea (CP-CRE) in the intensive care unit (ICU). Methods: All gram-negative isolates collected between November 2018 to April 2019 were tested for carbapenem resistance using the disc-diffusion method. Carbapenem-resistant bacteria, defined as meropenem resistant, were tested for phenotypic carbapenemase-production using the Becton Dickinson Phoenix CPO Detect assay. An intervention package, including placement of patients in cohorts, enhanced barrier precautions, enhanced discharge environmental cleaning, and CP-CRE rectal screening, was implemented from July 2019 through December 2020. During this period, all ICU patients were screened on admission, and negative patients were rescreened every 2 days or 7 days until discharge, death, or CRE-positive result. Admission prevalence and incidence of CP-CRE transmission was calculated among CP-CRE infected or colonized patients. Results: Among 599 gram-negative isolates collected, 108 were carbapenem-resistant isolates, of which 107 (99%) were CP-CRO by the phenotypic method. Most CP-CRO were Acinetobacter baumannii (42%) and Klebsiella pneumoniae (36%). Of 1,206 patients, 433 (35.9%) were already colonized or infected with CP-CRE before admission to the ICU. The incidence rate (cases per 100 risk days) of CP-CRE colonization or infection during ICU treatment decreased from 11.5 before the intervention to 2.9 after the implementation of the intervention package. The average number of days to change from a negative to positive screening result in the intervention phase was 7.4, compared with 4.9 days during preintervention phase. Conclusions: Nearly all CROs isolated from our ICU are carbapenemase-producing CROs, with high presence on admission as well as new acquisition during an ICU stay. An intervention package containing enhanced infection control measures was effective in reducing CP-CRE transmission.

Background: Insecticide resistance in malaria vectors can be spatially highly heterogeneous, yet population structure analyses frequently find relatively high levels of gene flow among mosquito populations. Few studies have contemporaneously assessed phenotypic, genotypic and population structure analysis on mosquito populations and none at fine geographical scales. In this study, genetic diversity, population structure, and insecticide resistance profiles of Anopheles funestus and Anopheles arabiensis were examined across mosquito populations from and within neighbouring villages. Methods: Mosquitoes were collected from 11 towns in southern Mozambique, as well as from different neighbourhoods within the town of Palmeira, during the peak malaria transmission season in 2016. CDC bottle bioassay and PCR assays were performed with Anopheles mosquitoes at each site to determine phenotypic and molecular insecticide resistance profiles, respectively. Microsatellite analysis was conducted on a subsample of mosquitoes to estimate genetic diversity and population structure. Results: Phenotypic insecticide resistance to deltamethrin was observed in An. funestus sensu stricto (s.s.) throughout the area, though a high level of mortality variation was seen. However, 98% of An. funestus s.s. were CYP6P9a homozygous resistant. An. arabiensis was phenotypically susceptible to deltamethrin and 99% were kdr homozygous susceptible. Both Anopheles species exhibited high allelic richness and heterozygosity. Significant deviations from Hardy-Weinberg equilibrium were observed, and high linkage disequilibrium was seen for An. funestus s.s., supporting population subdivision. However, the FST values were low for both anophelines (- 0.00457 to 0.04213), Nm values were high (9.4-71.8 migrants per generation), AMOVA results showed almost 100% genetic variation among and within individuals, and Structure analysis showed no clustering of An. funestus s.s. and An. arabiensis populations. These results suggest high gene flow among mosquito populations. Conclusion: Despite a relatively high level of phenotypic variation in the An. funestus population, molecular analysis shows the population is admixed. These data indicate that CYP6P9a resistance markers do not capture all phenotypic variation in the area, but also that resistance genes of high impact are likely to easily spread in the area. Conversely, other strategies, such as transgenic mosquito release programmes will likely not face challenges in this locality.

Background Preterm birth and resulting respiratory failure is a leading cause of newborn death- the majority of which occur in resource-constrained settings and could be prevented with bubble continuous positive airway pressure (bCPAP). Commercialized devices are expensive, however, and sites commonly use improvised devices utilizing 100% oxygen which can cause blindness. To address this, PATH and a multidisciplinary team developed a very low-cost bCPAP device including fixed-ratio oxygen blenders. Objective We assessed feasibility of use of the device on neonatal patients as well as the usability and acceptability of the device by healthcare workers. This study did not evaluate device effectiveness. Methods The study took place in a Ugandan level two unit. Neonates with respiratory failure were treated with the bCPAP device. Prospective data were collected through observation as well as likert-style scales and interviews with healthcare workers. Data were analyzed using frequencies, means and standard deviation and interviews via a descriptive coding method. Retrospectively registered via ClinicalTrials.gov number NCT05462509. Results Fourteen neonates were treated with the bCPAP device in October—December 2021. Patients were born onsite (57%), with median weight of 1.3 kg (IQR 1–1.8). Median treatment length was 2.5 days (IQR 2–6). bCPAP was stopped due to: improvement (83%) and death (17%). All patients experienced episodes of saturations >95%. Median time for device set up: 15 minutes (IQR 12–18) and changing the blender: 15 seconds (IQR 12–27). After initial device use, 9 out of 9 nurses report the set-up as well as blender use was “easy” and their overall satisfaction with the device was 8.5/10 (IQR 6.5–9.5). Interview themes included the appreciation for the ability to administer less than 100% oxygen, desire to continue use of the device, and a desire for additional blenders. Conclusions In facilities otherwise using 100% oxygen, use of the bCPAP device including oxygen blenders is feasible and acceptable to healthcare workers. Trial registration ClinicalTrials.gov, Identifier NCT05462509 .

Background: Attractive targeted sugar bait (ATSB) stations are a promising new approach to malaria vector control that could compliment current tools by exploiting the natural sugar feeding behaviors of mosquitoes. Recent proof of concept work with a prototype ATSB® Sarabi Bait Station (Westham Co., Hod-Hasharon, Israel) has demonstrated high feeding rates and significant reductions in vector density, human biting rate, and overall entomological inoculation rate for Anopheles gambiae sensu lato (s.l.) in the tropical savannah of western Mali. The study reported here was conducted in the more temperate, rainier region of Western Province, Zambia and was designed to confirm the primary vector species in region and to estimate corresponding rates of feeding from prototype attractive sugar bait (ASB) Sarabi Bait Stations. Methods: The product evaluated was the Sarabi v1.1.1 ASB station, which did not include insecticide but did include 0.8% uranine as a dye allowing for the detection, using UV fluorescence light microscopy, of mosquitoes that have acquired a sugar meal from the ASB. A two-phase, crossover study design was conducted in 10 village-based clusters in Western Province, Zambia. One study arm initially received 2 ASB stations per eligible structure while the other initially received 3. Primary mosquito sampling occurred via indoor and outdoor CDC Miniature UV Light Trap collection from March 01 through April 09, 2021 (Phase 1) and from April 19 to May 28, 2021 (Phase 2). Results: The dominant vector in the study area is Anopheles funestus s.l., which was the most abundant species group collected (31% of all Anophelines; 45,038/144,5550), had the highest sporozoite rate (3.16%; 66 positives out of 2,090 tested), and accounted for 94.3% (66/70) of all sporozoite positive specimens. Of those An. funestus specimens further identified to species, 97.2% (2,090/2,150) were An. funestus sensu stricto (s.s.). Anopheles gambiae s.l. (96.8% of which were Anopheles arabiensis) is a likely secondary vector and Anopheles squamosus may play a minor role in transmission. Overall, 21.6% (9,218/42,587) of An. funestus specimens and 10.4% (201/1,940) of An. gambiae specimens collected were positive for uranine, translating into an estimated daily feeding rate of 8.9% [7.7-9.9%] for An. funestus (inter-cluster range of 5.5% to 12.7%) and 3.9% [3.3-4.7%] for An. gambiae (inter-cluster range of 1.0-5.2%). Feeding rates were no different among mosquitoes collected indoors or outdoors, or among mosquitoes from clusters with 2 or 3 ASBs per eligible structure. Similarly, there were no correlations observed between feeding rates and the average number of ASB stations per hectare or with weekly rainfall amounts. Conclusions: Anopheles funestus and An. gambiae vector populations in Western Province, Zambia readily fed from the prototype Sarabi v1.1.1 ASB sugar bait station. Observed feeding rates are in line with those thought to be required for ATSB stations to achieve reductions in malaria transmission when used in combination with conventional control methods (IRS or LLIN). These results supported the decision to implement a large-scale, epidemiological cluster randomized controlled trial of ATSB in Zambia, deploying 2 ATSB stations per eligible structure.

Itezhi-Tezhi District in southern Zambia has been reporting tuberculosis (TB) mortality rates that are fourfold higher than the national average of six percent. We conducted a retrospective cohort study to establish the demographic and clinical characteristics associated with mortality among persons under treatment for TB in Itezhi-Tezhi District, as well as the likely causes and time to death. We reviewed medical records for persons with TB registered in 19 public health facilities in Itezhi-Tezhi District between January 2015 and December 2018. Of the 506 persons with TB registered in the study period, 426 were included in the analysis. Of these, 71 (16.7%) died before completing treatment. The overall mortality rate was 31.8 per 1,000 person-months of observation. Most of the deaths (53 [74.7%]) occurred in the first month of treatment (median: 16 days; interquartile range: 5–52 days). In a multivariate Cox regression model, type of TB was found to be an independent predictor of mortality while on TB treatment. The risk of dying was more than twice higher for persons with clinically diagnosed PTB compared to those with bacteriologically confirmed PTB (adjusted hazard ratio = 2.2, 95% CI: 1.4–3.6). In a sub-analysis of persons with clinically diagnosed PTB, persons with TB who were on a community-based DOT plan were more than twice more likely to die compared to those on facility-based DOT plan (adjusted hazard ratio = 2.21, 95% CI: 1.1–4.8). Common likely causes of death were pulmonary TB disease (66.0%), anemia (12.8%), cardiac failure (4.3%), pneumocystis jiroveci pneumonia (4.3%), and gastroenteritis (4.2%). These findings show that most deaths occurred during the first month of treatment. Clinical evaluation at initiation of anti-TB treatment and during follow-up care, especially in persons with clinically diagnosed PTB, should include screening and treatment of other conditions.

Prevalence of hypertension (HTN) and human immunodeficiency virus (HIV) are high among men while screening rates are low. Assisted partner notification service is a strategy recommended by the World Health Organization that aims to increase HIV testing and treatment uptake and may present an opportunity to offer integrated HIV/HTN screening and treatment services. In this prospective cohort study, we assessed the feasibility of integrating HTN screening for male sexual partners of females newly tested HIV-positive in 10 health facilities in Kenya. Participants were notified of the exposure and offered HIV testing and HTN screening; if they accepted and tested positive for either HTN, HIV, or both, they were referred for care. HTN was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90, or the use of antihypertensive medication. Among 1313 male partners traced, 99% accepted HIV testing and HTN screening. Overall, 4% were found to have HTN, 29% were in the pre-HTN stage, and 9% were HIV-positive. Only 75% had previously been screened for HTN compared to 95% who had previously tested for HIV. A majority preferred non-facility-based screening. The participants who refused HTN screening noted time constraints as a significant hindrance. HIV and HTN screening uptake was high in this hard-to-reach population of men aged 25 to 50. Although HTN rates were low, an integrated approach provided an opportunity to detect those with pre-HTN and intervene early. Strategic integration of HTN services within assisted partners services may promote and normalize testing by offering inclusive and accessible services to men.

Background A minimum of one ultrasound scan is recommended for all pregnant women before the 24th week of gestation. In Ethiopia, there is a shortage of skilled manpower to provide these services. Currently, trained mid-level providers are providing the services at the primary healthcare level. The aims of this study were to compare antenatal care 1 (ANC1), antenatal care 4 (ANC4), skilled birth attendance (SBA), and postnatal care (PNC) service utilization before and after institutionalizing Vscan limited obstetric ultrasounds at semi-urban health centers in Ethiopia. Methods A pre and post intervention observational study was conducted to investigate maternal and neonatal health service utilization rates before and after institutionalizing Vscan limited obstetric ultrasound services, between July 2016 and June 2020. The data were extracted from 1st August– 31st December 2020. Results The observed monthly increase on the mean rank of first ANC visits after the introduction of Vscan limited obstetric ultrasound services showed a statistically significant difference at KW-ANOVA H (3) = 17.09, P = 0.001. The mean rank of fourth ANC utilization showed a statistically significant difference at KW- ANOVA H (3) = 16.24, P = 0.001. The observed mean rank in skilled birth attendance (SBA) showed a statistically significant positive difference using KW-ANOVA H (3) = 23.6, P<0.001. The mean rank of increased utilization in postnatal care showed a statistically significant difference using KW-ANOVA H (3) = 17.79, P<0.001. Conclusion The introduction of limited obstetric ultrasound services by trained mid-level providers at the primary healthcare level was found to have improved the utilization of ANC, SBA, and postnatal care (PNC) services. It is recommended that the institutionalization of limited obstetric ultrasound services be scaled up and a further comparative study between facilities with and without ultrasound services be conducted to confirm causality and assess effects on maternal and perinatal outcomes.

NDV-HXP-S is a recombinant Newcastle disease virus-based vaccine against SARS-CoV-2, which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that used for the production of the vast majority of influenza virus vaccines. Here, we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a phase 1 clinical study in Thailand. The SARS-CoV-2 neutralizing and spike protein binding activity of NDV-HXP-S postvaccination serum samples was compared to that of samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of BNT162b2 vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccinees. This led us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios that were lower than those of BNT162b2 sera, suggesting that NDV-HXP-S vaccination elicits a high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induced an RBD-focused antibody response with little reactivity to S2. This finding may explain the high proportion of neutralizing antibodies. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers that are comparable to those elicited by mRNA vaccination.

Objectives To describe the feeding profile of low birthweight (LBW) infants in the first half of infancy; and to examine growth patterns and early risk factors of poor 6-month growth outcomes. Design Prospective observational cohort study. Setting and participants Stable, moderately LBW (1.50 to <2.50 kg) infants were enrolled at birth from 12 secondary/tertiary facilities in India, Malawi and Tanzania and visited nine times over 6 months. Variables of interest Key variables of interest included birth weight, LBW type (combination of preterm/term status and size-for-gestational age at birth), lactation practices and support, feeding profile, birthweight regain by 2 weeks of age and poor 6-month growth outcomes. Results Between 13 September 2019 and 27 January 2021, 1114 infants were enrolled, comprising 4 LBW types. 363 (37.3%) infants initiated early breast feeding and 425 (43.8%) were exclusively breastfed to 6 months. 231 (22.3%) did not regain birthweight by 2 weeks; at 6 months, 280 (32.6%) were stunted, 222 (25.8%) underweight and 88 (10.2%) wasted. Preterm-small-for-gestational age (SGA) infants had 1.89 (95% CI 1.37 to 2.62) and 2.32 (95% CI 1.48 to 3.62) times greater risks of being stunted and underweight at 6 months compared with preterm-appropriate-for-gestational age (AGA) infants. Term-SGA infants had 2.33 (95% CI 1.77 to 3.08), 2.89 (95% CI 1.97 to 4.24) and 1.99 (95% CI 1.13 to 3.51) times higher risks of being stunted, underweight and wasted compared with preterm-AGA infants. Those not regaining their birthweight by 2 weeks had 1.51 (95% CI 1.23 to 1.85) and 1.55 (95% CI 1.21 to 1.99) times greater risks of being stunted and underweight compared with infants regaining. Conclusion LBW type, particularly SGA regardless of preterm or term status, and lack of birthweight regain by 2 weeks are important risk identification parameters. Early interventions are needed that include optimal feeding support, action-oriented growth monitoring and understanding of the needs and growth patterns of SGA infants to enable appropriate weight gain and proactive management of vulnerable infants. Trial registration number NCT04002908 .

Introduction: Market size estimations and demand forecasts use a variety of methodological approaches to inform decision-making around new (and lesser-used) contraceptive methods. For contraceptive products already available at scale in a market, historical procurement and consumption data can help to inform these forecasts. However, little published guidance is available on appropriate approaches to estimating contraceptive demand in the absence of historical data. Methods: This landscape review aimed to describe the variety of approaches for modeling demand for new contraceptive methods, highlight opportunities for alignment around forecasting practices, and make recommendations to support more accurate forecasting and sound decision-making based on forecasts. We used the published scientific and gray literature to inform the development of a semistructured guide for key informant interviews. We conducted interviews with 29 experts representing a spectrum of interests in market size estimation and demand forecasting for new contraceptive methods (e.g., ministries of health, donors, manufacturers, technical assistance providers, and demand forecasting specialists). We coded notes from the interviews using thematic content analysis. Results: The purposes of market size estimation and demand forecasting for new contraceptive methods vary widely, as do associated model inputs and outputs. Key informants revealed a need for more standardized language around market size estimation and demand forecasting and highlighted key recommendations: select models that are fit-for-purpose, clearly articulate assumptions and uncertainty in model outputs, consider a broad range of contraceptive options in a forecast to capture the complete contraceptive supply environment, and perform a reality check of results and refresh assumptions. Conclusion: We recommend following a simple decision pathway to ensure that forecasts are fit-for-purpose, with appropriate inputs, outputs, and assumptions clearly articulated. Common pitfalls around overestimating demand should be avoided. Incorporating best practices into forecasting exercises will ensure that models are useful for the stakeholders.

Background Little information is available on the costs of respiratory syncytial virus (RSV) in Vietnam or other low- and middle-income countries. Our study estimated the costs of LRTIs associated with RSV infection among children in southern Vietnam. Methods We conducted a prospective cohort study evaluating household and societal costs associated with LRTIs stratified by RSV status and severity among children under 2 years old who sought care at a major pediatric referral hospital in southern Vietnam. Enrollment periods were September 2019–December 2019, October 2020–June 2021 and October 2021–December 2021. RSV status was confirmed by a validated RT-PCR assay. RSV rapid detection antigen (RDA) test performance was also evaluated. Data on resource utilization, direct medical and non-medical costs, and indirect costs were collected from billing records and supplemented by patient-level questionnaires. All costs are reported in 2022 US dollars. Results 536 children were enrolled in the study, with a median age of 7 months (interquartile range [IQR] 3–12). This included 210 (39.2%) children from the outpatient department, 318 children (59.3%) from the inpatient respiratory department (RD), and 8 children (1.5%) from the intensive care unit (ICU). Nearly 20% (105/536) were RSV positive: 3.9 percent (21/536) from the outpatient department, 15.7% (84/536) from the RD, and none from the ICU. The median total cost associated with LRTI per patient was US$52 (IQR 32–86) for outpatients and US$184 (IQR 109–287) for RD inpatients. For RSV-associated LRTIs, the median total cost per infection episode per patient was US$52 (IQR 32–85) for outpatients and US$165 (IQR 95–249) for RD inpatients. Total out-of-pocket costs of one non-ICU admission of RSV-associated LRTI ranged from 32%-70% of the monthly minimum wage per person (US$160) in Ho Chi Minh City. The sensitivity and the specificity of RSV RDA test were 88.2% (95% CI 63.6–98.5%) and 100% (95% CI 93.3–100%), respectively. Conclusion These are the first data reporting the substantial economic burden of RSV-associated illness in young children in Vietnam. This study informs policymakers in planning health care resources and highlights the urgency of RSV disease prevention.

Objectives Use of intrauterine balloon tamponades for refractory postpartum haemorrhage (PPH) management has triggered recent debate since effectiveness studies have yielded conflicting results. Implementation research is needed to identify factors influencing successful integration into maternal healthcare packages. The Ellavi uterine balloon tamponade (UBT) (Ellavi) is a new low-cost, preassembled device for treating refractory PPH. Design A mixed-methods, prospective, implementation research study examining the adoption, sustainability, fidelity, acceptability and feasibility of introducing a newly registered UBT. Cross-sectional surveys were administered post-training and post-use over 10 months. Setting Three Ghanaian (district, regional) and three Kenyan (levels 4–6) healthcare facilities. Participants Obstetric staff (n=451) working within participating facilities. Intervention PPH management training courses were conducted with obstetric staff. Primary and secondary outcome measures Facility measures of adoption, sustainability and fidelity and individual measures of acceptability and feasibility. Results All participating hospitals adopted the device during the study period and the majority (52%–62%) of the employed obstetric staff were trained on the Ellavi; sustainability and fidelity to training content were moderate. The Ellavi was suited for this context due to high delivery and PPH burden. Dynamic training curriculums led by local UBT champions and clear instructions on the packaging yielded positive attitudes and perceptions, and high user confidence, resulting in overall high acceptability. Post-training and post-use, ≥79% of the trainees reported that the Ellavi was easy to use. Potential barriers to use included the lack of adjustable drip stands and difficulties calculating bag height according to blood pressure. Overall, the Ellavi can be feasibly integrated into PPH care and was preferred over condom catheters. Conclusions The training package and time saving Ellavi design facilitated its adoption, acceptability and feasibility. The Ellavi is appropriate and feasible for use among obstetric staff and can be successfully integrated into the Kenyan and Ghanaian maternal healthcare package. Trial registration numbers NCT04502173 ; NCT05340777 .

Background In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programmes’ elimination efforts. A better understanding of forest-going populations’ mobility patterns and risk associated with specific types of forest-going trips is necessary for countries in the GMS to achieve their objective of eliminating malaria by 2030. Methods Between March and November 2018, as part of a focal test and treat intervention (FTAT), 2,904 forest-goers were recruited in southern Lao PDR. A subset of forest-goers carried an “i-Got-U” GPS logger for roughly 2 months, configured to collect GPS coordinates every 15 to 30 min. The utilization distribution (UD) surface around each GPS trajectory was used to extract trips to the forest and forest-fringes. Trips with shared mobility characteristics in terms of duration, timing and forest penetration were identified by a hierarchical clustering algorithm. Then, clusters of trips with increased exposure to dominant malaria vectors in the region were further classified as high-risk. Finally, gradient boosting trees were used to assess which of the forest-goers’ socio-demographic and behavioural characteristics best predicted their likelihood to engage in such high-risk trips. Results A total of 122 forest-goers accepted carrying a GPS logger resulting in the collection of 803 trips to the forest or forest-fringes. Six clusters of trips emerged, helping to classify 385 (48%) trips with increased exposure to malaria vectors based on high forest penetration and whether the trip happened overnight. Age, outdoor sleeping structures and number of children were the best predictors of forest-goers’ probability of engaging in high-risk trips. The probability of engaging in high-risk trips was high (~ 33%) in all strata of the forest-going population. Conclusion This study characterized the heterogeneity within the mobility patterns of forest-goers and attempted to further segment their role in malaria transmission in southern Lao People’s Democratic Republic (PDR). National control programmes across the region can leverage these results to tailor their interventions and messaging to high-risk populations and accelerate malaria elimination.

HIV self-testing (HIVST) is an effective approach to increase testing uptake. While oral fluid-based HIVST has been rapidly scaled, use of blood-based HIVST remains limited. We evaluated the acceptability, feasibility, and accuracy of blood-based HIVST among lay users in Ho Chi Minh City (HCMC), Vietnam. We conducted a cross-sectional study among HIV testing clients at the HCMC Pasteur Institute from March 2019 to October 2020. Participants received one HIVST kit and performed the test in front of an observer. The observer used product-specific questionnaires to collect information on the HIVST process, test results, experiences. The participants’ interpretations of HIVST results were compared to health staff’s interpretations and gold standard laboratory EIA reference tests. Of 2,399 participants who accepted HIVST, 64.7% were men, 62.1% aged 25–49 years, 53.5% had a higher education level, 41.4% were employed, and 35.6% were first-time testers. The vast majority (94.4%) desired to use the test in the future, and 93.9% reported willingness to recommend the test. The majority (90.8%) of participants successfully completed the self-test. One factor associated with successful completion was higher education level (aOR = 1.85; 95% CI: 1.32–2.61); while participants self-testing with SURE CHECK (aOR = 0.21; 95% CI: 0.12–0.37), INSTI (aOR = 0.23; 95% CI: 0.13–0.39), and BioSURE (aOR = 0.29; 95% CI: 0.17–0.51) or being unemployed, retired, or doing housework (aOR = 0.45; 95% CI: 0.25–0.82) were less likely to perform the test successfully. Agreement of positive and negative HIVST results as interpreted by participants and health staff was high (98.1% and 99.9%, respectively). Sensitivity and specificity of the evaluated HIVST were 96.43% (95% CI: 93.62–99.23) and 99.9% (95% CI: 99.75–100), respectively. Our findings confirm that blood-based HIVST is highly acceptable, feasible, and accurate. This evidence informs scale-up of HIVST to increase uptake of essential HIV prevention and treatment services.

Vaccine packaging innovations have a potential impact on the supply chain, from factory to vaccination sites in low‐ and middle‐income countries, as well as acceptability and uptake by users. To better understand recent developments in packaging innovations, we assessed the benefits and challenges of compact pre‐filled auto‐disable devices (CPADs), polymer‐based primary containers (or vials), and dual‐chamber delivery devices. These packaging innovations have clear public health benefits related to ease of use, improved safety, supply logistics, and uptake enabling new vaccination opportunities. In addition, there seems to be high acceptability from users at country‐level. However, uncertain costs including the impact on distribution and cold chain storage have hampered demand and consequently commercialization. For innovations to reach those who can benefit most, global stakeholders should place greater attention on new packaging technologies and assess the trade‐offs between safety, coverage, uptake, ease of administration, wastage and costs. This article is protected by copyright. All rights reserved.

A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not efficacy in animal models. Here we assessed formulations identified to improve or reduce stability of the mucosal adjuvant dmLT being investigated in polio and enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes to dmLT protein with formulation or thermal stress, including aggregation or subunit dissociation or alternatively resistance against these changes with specific buffer compositions. However, upon injection or mucosal vaccination with ETEC fimbriae adhesin proteins or inactivated polio virus, experimental findings indicated immunization route and co-administered antigen impacted vaccine immunogenicity more so than dmLT formulation stability (or instability). These results indicate the importance of both biochemical and vaccine-derived immunity assessment in formulation optimization. In addition, these studies have implications for use of dmLT in clinical settings and for delivery in resource poor settings.

Introduction: There is growing interest among low- and middle-income countries to introduce electronic immunization registries (EIRs) that capture individual-level vaccine data. We compare the design, development, and deployment of EIRs in Vietnam, Tanzania, and Zambia. Through desk review and the authors' firsthand implementation experiences, we describe experiences related to timeline, partnerships, financial costs, and technology and infrastructure. Implementation experience: The country cases highlight the multi-year timeline required to implement an EIR at scale and the benefit of multiple iterative cycles to pilot and redesign the system before achieving scale. Of the 3 countries, only Vietnam has achieved nationwide scale of the EIR, which took 7 years. In all 3 countries, national government leadership as part of an interdisciplinary team (with experience in leadership, technology, and immunization) was important to ensure country ownership and sustainability. Where international software developers were contracted, partnering with a local software company helped improve responsiveness and sustainability. Across all 3 countries, governments contributed significant in-kind time in addition to investments from donors. Cost savings were observed in Tanzania and Zambia, largely driven by health worker time savings from using the EIR. All 3 case countries underscore the need to understand the local technology and infrastructure context and design the EIR to fit the context. In Vietnam, an initial landscape assessment was conducted to assess technology and infrastructure, whereas in Tanzania and Zambia, user advisory groups provided insights. Existing infrastructure informed EIR design decisions, such as choosing a system with offline functionality in Tanzania and Zambia. All 3 countries have a local partner to provide ongoing technical support. Conclusion: Comparing implementation factors across these cases highlights practical experience and recommendations that complement existing EIR guidance documents. The findings and recommendations from this study can inform other countries considering or in the process of implementing an EIR.

Efforts to eliminate vector-borne diseases, for example malaria which caused an estimated 619,000 deaths in 2021 [...]