RTS,S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by the World Health Organization (WHO). Trials reported lower vaccine efficacies in ...higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies.
Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambaréné, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with 3-way interactions between vaccination, time, and transmission intensity.
Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest-transmission-intensity group (0.25 cases per person-year CPPY) decreased from 88.2% to 15.0% over 4.5 years, compared with 81.6% to -27.7% in the highest-transmission-intensity group (3 CPPY).
These findings suggest that interventions, including the fourth RTS,S dose, that protect vaccinated individuals during the potential rebound period should be implemented for high-transmission settings.
RTS,S/AS01, the most advanced vaccine against malaria, is now undergoing pilot implementation in Malawi, Ghana, and Kenya where an estimated 360,000 children will be vaccinated each year. In this ...study we evaluate RTS,S/AS01 alongside bed net use and estimate cost-effectiveness.
RTS,S/AS01 phase III trial and bed net prevalence data were used to determine the effect of vaccination in the urban/periurban and rural areas of Lilongwe, Malawi. Cost data were used to calculate the cost-effectiveness of various interventions over three years.
Since bed nets reduce malaria incidence and homogeneous vaccine efficacy was assumed, participants without bed nets received greater relative benefit from vaccination with RTS,S/AS01 than participants with bed nets. Similarly, since malaria incidence in rural Lilongwe is higher than in urban Lilongwe, the impact and cost-effectiveness of vaccine interventions is increased in rural areas. In rural Lilongwe, we estimated that vaccinating one child without a bed net would prevent 2·59 (1·62 to 3·38) cases of malaria over three years, corresponding to a cost of $10·08 (7·71 to 16·13) per case averted. Alternatively, vaccinating one child with a bed net would prevent 1·59 (0·87 to 2·57) cases, corresponding to $16·43 (10·16 to 30·06) per case averted. Providing RTS,S/AS01 to 30,000 children in rural Lilongwe was estimated to cost $782,400 and to prevent 58,611 (35,778 to 82,932) cases of malaria over a three-year period. Joint interventions providing both vaccination and bed nets (to those without them) were estimated to prevent additional cases of malaria and to be similarly cost-effective, compared to vaccine-only interventions.
To maximize malaria prevention, vaccination and bed net distribution programs could be integrated.
Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy (1R01AI137410-01)
A lumbar puncture (LP) procedure plays a key role in meningitis diagnosis. In Malawi and other sub-Saharan African countries, LP completion rates are sometimes poor, making meningitis surveillance ...challenging. Our objective was to measure LP rates following an intervention to improve these during a sentinel hospital meningitis surveillance exercise in Malawi.
We conducted a before/after intervention analysis among under-five children admitted to paediatric wards at four secondary health facilities in Malawi. We used local and World Health Organization (WHO) guidelines to determine indications for LP, as these are widely used in low- and middle-income countries (LMIC). The intervention comprised of refresher trainings for facility staff on LP indications and procedure, use of automated reminders to perform LP in real time in the wards, with an electronic data management system, and addition of surveillance-specific clinical officers to support existing health facility staff with performing LPs. Due to the low numbers in the before/after analysis, we also performed a during/after analysis to supplement the findings.
A total of 13,375 under-five children were hospitalised over the 21 months window for this analysis. The LP rate was 10.4% (12/115) and 60.4% (32/53) in the before/after analysis, respectively, and 43.8% (441/1006) and 72.5% (424/599) in the supplemental during/after analysis, respectively. In our intervention-specific analysis among the three individual components, there were improvements in the LP rate by 48% (p < 0.001) following the introduction of surveillance-specific clinical officers, 10% (p < 0.001) following the introduction of automated reminders to perform an LP and 13% following refresher training.
This analysis demonstrated a rise in LP rates following our intervention. This intervention package may be considered for planning future facility-based meningitis surveillances in similar low-resource settings.
Objective
Globally, early and optimal feeding practices and strategies for small and vulnerable infants are limited. We aim to share the challenges faced and implementation lessons learned from a ...complex, mixed methods research study on infant feeding.
Design
A formative, multi‐site, observational cohort study using convergent parallel, mixed‐methods design.
Setting
Twelve tertiary/secondary, public/private hospitals in India, Malawi and Tanzania.
Population or Sample
Moderately low birthweight infants (MLBW; 1.50–2.49 kg).
Methods
We assessed infant feeding and care practices through: (1) assessment of in‐facility documentation of 603 MLBW patient charts; (2) intensive observation of 148 MLBW infants during facility admission; and (3) prospective 1‐year follow‐up of 1114 MLBW infants. Focus group discussions and in‐depth interviews gathered perspectives on infant feeding among clinicians, families, and key stakeholders.
Main Outcome Measures
The outcomes of the primary study were: (1) To understand the current practices and standard of care for feeding LBW infants; (2) To define and document the key outcomes (including growth, morbidity, and lack of success on mother's own milk) for LBW infants under current practices; (3) To assess the acceptability and feasibility of a system‐level Infant and Young Child Feeding (IYCF) intervention and the proposed infant feeding options for LBW infants.
Results
Hospital‐level guidelines and provision of care for MLBW infants varied across and within countries. In all, 89% of charts had missing data on time to first feed and 56% lacked discharge weights. Among 148 infants observed in‐facility, 18.5% were discharged prior to meeting stated weight goals. Despite challenges during COVID, 90% of the prospective cohort was followed until 12 months of age.
Conclusions
Enrolment and follow‐up of this vulnerable population required additional effort from researchers and the community. Using a mixed‐methods exploratory study allowed for a comprehensive understanding of MLBW health and evidence‐based planning of targeted large‐scale interventions. Multi‐site partnerships in global health research, which require active and equal engagement, are instrumental in avoiding duplication and building a stronger, generalisable evidence base.
To assess the association between breastfeeding competency, as determined by Latch, Audible swallowing, Type of nipple, Comfort, and Hold (LATCH) and Preterm Infant Breastfeeding Behavior Scale ...(PIBBS) scores, and exclusive breastfeeding and growth among infants with low birth weight (LBW) in India, Malawi, and Tanzania.
We conducted LATCH and PIBBS assessments among mother-infant dyads enrolled in the Low Birthweight Infant Feeding Exploration (LIFE) observational study of infants with moderately LBW (1500g-2499 g) in India, Malawi, and Tanzania. We analyzed feeding and growth patterns among this cohort.
We observed 988 infants. We found no association between LATCH or PIBBS scores and rates of exclusive breastfeeding at 4 or 6 months. Higher week 1 LATCH and PIBBS scores were associated with increased likelihood of regaining birth weight by 2 weeks of age LATCH: aRR 1.42 (95% CI 1.15, 1.76); PIBBS: aRR 1.15 (95% CI 1.07, 1.23); adjusted for maternal age, parity, education, residence, delivery mode, LBW type, number of offspring, and site. Higher PIBBS scores at 1 week were associated with improved weight gain velocity (weight-for-age z-score change) at 1, 4, and 6 months adjusted beta coefficient: 1 month 0.04 (95% CI 0.01, 0.06); 4 month 0.04 (95% CI 0.01, 0.06); and 6 month 0.04 (95% CI 0.00, 0.08).
Although week 1 LATCH and PIBBS scores were not associated with rates of exclusive breastfeeding, higher scores were positively associated with growth metrics among infants with LBW, suggesting that these tools may be useful to identify dyads who would benefit from early lactation support.
Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica ...serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures.
Introduction
Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub‐Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to ...limited region‐specific evidence for safety and efficacy.
Methods
We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi. From January 2015 to November 2017, hydroxyurea at doses of 10–20 mg/kg/day was administered to children with clinically severe disease (targeted use policy). From December 2017 to July 2018, hydroxyurea was prescribed to all patients (universal use policy).
Results
Of 187 patients with SCD, seven (3.7%) died and 23 (12.3%) were lost to follow‐up. The majority (135, 72.2%) were prescribed hydroxyurea, 59 (43.7%) under the targeted use policy and 76 (56.3%) under the universal use policy. There were no documented severe toxicities. Under the targeted use policy, children with SCD demonstrated absolute decreases in the rates of hospitalization (−4.1 per 1000 person‐days; −7.2, −1.0; P = .004), fevers (−4.2 per 1000 person‐days; −7.2, −1.1; P = .002), transfusions (−2.3 per 1000 person‐days; 95% confidence interval: −4.9, 0.3; P = .06), and annual school absenteeism (−51.2 per person‐year; −60.1, −42.3; P < .0001) within 6 months of hydroxyurea commencement.
Conclusion
We successfully implemented universal administration of hydroxyurea to children with SCD at a tertiary hospital in Malawi. Similar to recently reported trials, hydroxyurea was safe and effective during routine programmatic experience, with clinical benefits particularly among high‐risk children. This highlights the importance of continued widespread scale‐up of hydroxyurea within SCD programs across SSA.
Objective
To assess the performance of reusable pulse oximeter probe and microprocessor box combinations, of varying price‐points, in the context of a low‐income pediatric setting.
Methods
A ...prospective, randomized cross‐over study comparing time to biologically plausible oxygen saturation (SpO2) between: (1) Lifebox LB‐01 probe with Masimo Rad‐87 box (L + M) and (2) a weight‐appropriate reusable Masimo probe with Masimo Rad‐87 box (M + M). A post hoc secondary analysis comparison with historical usability testing data with the Lifebox LB‐01 probe and Lifebox V1.5 box (L + L) was also conducted. Participants, children aged 0 to 35 months, were recruited from pediatric wards and outpatient clinics in the central region of Malawi. The primary outcome was time taken to achieve a biologically plausible SpO
2 measurement, compared using t tests for equivalence.
Results
We recruited 572 children. Plausible SpO2 measurements were obtained in less than 1 minute, 71%, 70%, and 63% for the M + M, L + M, and L + L combinations, respectively. A similar pattern was seen for less than 2 minutes, however, this effect disappeared at less than 5 minutes with 96%, 96%, and 95% plausible measurements. Using a ±10 second threshold for equivalence, we found L + M and M + M to be equivalent, but were under‐powered to assess equivalence for L + L.
Conclusions
The novel reusable pediatric Lifebox probe can achieve a quality SpO2 measurement within a pragmatic time range of weight‐appropriate Masimo equivalent probes. Further research, which considers the cost of the devices, is needed to assess the added value of sophisticated motion tolerance software.
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