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The Oxford based OHSCAR team is delighted to be a partner the NEST360 project working with KEMRI-Wellcome and the Kenya Paediatric Research Consortium in Kenya to support this effort to improve care care of the sick newborn and save lives
Paediatric anaemia in rural Kenya and the role of travel time to emergency care services.
BACKGROUND: Access to emergency care (EC) services is crucial for severe anaemia outcome. Limited information exists on the association between travel times to EC services and the presentation and severity of anaemia upon hospital admission. Here, we investigate the association between travel time and presentation of severe anaemia (compared to mild/moderate anaemia) at admission in western Kenya. METHODS: Data from January 2020 to July 2023 from Busia County Referral Hospital were assembled for paediatric admissions aged 1-59 months residing in Busia County. Travel time from a patient's village to the hospital was calculated using a least cost path algorithm. Anaemia severity was categorised as mild (Hb ≥ 7-<10 g dl-1), moderate (Hb ≥ 5-<7 g dl-1) and severe (Hb
Community perspectives of heat and weather warnings for pregnant and postpartum women in Kilifi, Kenya
Background Extreme weather is a recognised risk factor for stillbirth and preterm birth, disrupts women’s access to healthcare during pregnancy and childbirth, and negatively affects the care of newborns. Reliable and accessible heat and weather warning systems are key in alerting individuals to undertake protective measures. There is a notable gap in understanding how women and caregivers in rural East Africa perceive and utilize weather information. We investigated community members’ heat and weather warning information-seeking behaviour, identified available sources, assessed their reliability and utility, and examined their influence on behaviour. Settings Our research was conducted in rural Kilifi County in Kenya’s coastal region. The area experiences temperatures exceeding 23°C throughout the year, with extended periods of extreme temperatures [> 40°C] and long and severe droughts. Methods We conducted in-depth interviews [IDI] with pregnant and postpartum women [n = 21] and held six focus group discussions [FGDs] involving mothers-in-law and community health volunteers [CHVs]. The data were analysed in NVivo 12 using both inductive and deductive approaches. Results We found significant gaps concerning pregnant and post-partum women, and their caregivers, having timely access to weather forecasts and heat information from health or meteorological authorities. Information on heat and weather warnings is disseminated through various channels, including television, radio, mobile phones, and word of mouth, which are facilitated by community influencers such as CHVs and local chiefs. Indigenous methods of weather forecasting, such as cloud observation, consulting local “rainmakers”, and studying the behavioural patterns of amphibians, are employed in conjunction with warnings from the Kenyan Meteorological Department (KMD). Barriers to accessing weather information include the cost of television and smartphones and a lack of segmented information in local languages. Conclusions National and county meteorological services need to enhance public participation, communication, and the delivery of heat and weather information to guide community-level response measures and individual behaviour change. They should also collaborate with health professionals to address heat risks for vulnerable groups. Further research is needed to empower indigenous weather predictors with modern weather information and revise national policies to deliver tailored messages to vulnerable populations like pregnant and postpartum women.
Community perspectives of heat and weather warnings for pregnant and postpartum women in Kilifi, Kenya
Extreme weather is a recognised risk factor for stillbirth and preterm birth, disrupts women’s access to healthcare during pregnancy and childbirth, and negatively affects the care of newborns. Reliable and accessible heat and weather warning systems are key in alerting individuals to undertake protective measures. There is a notable gap in understanding how women and caregivers in rural East Africa perceive and utilize weather information. We investigated community members’ heat and weather warning information-seeking behaviour, identified available sources, assessed their reliability and utility, and examined their influence on behaviour. Our research was conducted in rural Kilifi County in Kenya’s coastal region. The area experiences temperatures exceeding 23°C throughout the year, with extended periods of extreme temperatures [> 40°C] and long and severe droughts. We conducted in-depth interviews [IDI] with pregnant and postpartum women [n = 21] and held six focus group discussions [FGDs] involving mothers-in-law and community health volunteers [CHVs]. The data were analysed in NVivo 12 using both inductive and deductive approaches. We found significant gaps concerning pregnant and post-partum women, and their caregivers, having timely access to weather forecasts and heat information from health or meteorological authorities. Information on heat and weather warnings is disseminated through various channels, including television, radio, mobile phones, and word of mouth, which are facilitated by community influencers such as CHVs and local chiefs. Indigenous methods of weather forecasting, such as cloud observation, consulting local “rainmakers”, and studying the behavioural patterns of amphibians, are employed in conjunction with warnings from the Kenyan Meteorological Department (KMD). Barriers to accessing weather information include the cost of television and smartphones and a lack of segmented information in local languages. National and county meteorological services need to enhance public participation, communication, and the delivery of heat and weather information to guide community-level response measures and individual behaviour change. They should also collaborate with health professionals to address heat risks for vulnerable groups. Further research is needed to empower indigenous weather predictors with modern weather information and revise national policies to deliver tailored messages to vulnerable populations like pregnant and postpartum women.
Long-term retention and positive deviant practices in Uganda’s community client-led antiretroviral distribution groups (CCLADs): a mixed-methods study
BackgroundHIV testing and starting antiretroviral therapy (ART) are pivotal in treating people living with HIV (PLHIV) but sustaining PLHIV on treatment remains challenging. We assessed retention and attrition in community client-led antiretroviral distribution groups (CCLADs) in Uganda and identified positive deviant practices that foster long-term retention.MethodsUsing explanatory mixed methods, we collected longitudinal medical data from 65 health facilities across 12 districts in East Central Uganda. Quantitative phase, from 18 April 2021 to 30 May 2021, employed survival analysis and Cox regression to assess retention and identify attrition risk factors. Qualitative inquiry focused on four districts with high attrition from 11 August 2021 to 20 September 2021, where we identified nine health facilities exhibiting high retention in CCLADs. We purposively selected 50 clients for in-depth interviews (n=22) or focus group discussions (n=28). Using thematic analysis, we identified positive deviant practices. We integrated quantitative and qualitative findings into joint displays.ResultsInvolving 3055 PLHIV, the study showed retention rates of 97.5% at 6 months, declining to 89.7% at 96 months. Attrition risk factors were lower levels of care (health centre three (adjusted HR (aHR) 2.80, 95% CI 2.00 to 3.65) and health centre four (aHR 3.61, 95% CI 2.35 to 5.54)); being unemployed (aHR 2.21, 95% CI 1.00 to 4.84); enrolment year into CCLAD (aHR 23.93, 95% CI 4.66 to 123.05) and virological failure (aHR 3.41, 95% CI 2.51 to 4.63). Of 22 clients interviewed, 8 were positive deviants. Positive deviants were characterised by prolonged retention in CCLADs, improved clinical outcomes and practised uncommon behaviours that enabled them to find better solutions than their peers. Positive deviant practices included fostering family-like settings, offering financial or self-development advice, and promoting healthy lifestyles.ConclusionsFindings underscore the importance of addressing factors contributing to attrition and leveraging positive deviant practices to optimise retention and long-term engagement in HIV care.
The limitations of mobile phone data for measuring movement patterns of populations at risk of malaria.
BACKGROUND: As global mobile phone adoption increases, mobile phone data has been increasingly used to measure movement patterns of populations at risk of malaria. However, the representativeness of mobile phone data for populations at risk of malaria has not been assessed. This study aimed to assess this representativeness using prospectively collected data on mobile phone ownership and use from malaria patients in Lao PDR. METHODS: A prospective observational study was conducted from 2017 to 2021. 6320 patients with confirmed malaria in 107 health facilities in the five southernmost provinces of Lao PDR were surveyed regarding their demographics, mobile phone ownership and use. Data on the demographics of mobile phone owners and users in the general population of Lao PDR were obtained from the 2017 Lao Social Indicator Survey II, which was a nationally representative survey sample. Descriptive analysis was performed, and logistic regression with weights on aggregate data was used to compare the demographic distribution of mobile phone ownership and use in malaria patients with that in the general population. RESULTS: Most patients with malaria (76%) did not own or use a mobile phone. From 2017 to 2021, mobile phone usage in the general population consistently ranged between 53 and 67%, whereas among malaria patients, usage remained significantly lower, fluctuating between 20 and 28%. At the district level, log malaria incidence rate (API) was weakly negatively correlated with the proportion of mobile owners (R2 = 0.3, p = 0.005). Mobile phone ownership and usage among malaria patients were significantly lower than in the general population (p-value
Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY)
Background: Sotrovimab is a neutralising monoclonal antibody targeting the SARS-COV-2 spike protein that was evaluated in the RECOVERY trial, a randomised, controlled, open-label, platform trial testing treatments for COVID-19. Methods: Patients hospitalised with COVID-19 pneumonia from 107 UK hospitals were randomly allocated to either usual care alone or usual care plus a single 1g infusion of sotrovimab, using web-based unstratified randomisation. Participants were retrospectively categorised as ‘high-antigen’ (the prespecified primary analysis population) if baseline serum SARS-CoV-2 nucleocapsid antigen was above the median concentration, and otherwise as ‘low-antigen’. The primary outcome was 28-day mortality assessed by intention to treat. Recruitment closed on 31 March 2024 when funding ended. ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: From 4 January 2022 to 19 March 2024, 1723 patients were recruited, 828 allocated sotrovimab and 895 allocated usual care. 720 (42%) were classified as high-antigen, 717 (42%) as low-antigen, and 286 (17%) had unknown antigen status. 1389 (81%) patients were vaccinated, 1179/1438 with known serostatus (82%) had anti-spike antibodies at randomisation, and almost all were infected with Omicron variants. Among high-antigen patients, 82/355 (23%) allocated sotrovimab versus 106/365 (29%) allocated usual care died within 28 days (rate ratio 0.75; 95% CI 0.56-0.99; p=0.046). In an analysis of all randomised patients (regardless of antigen status), 177/828 (21%) allocated sotrovimab versus 201/895 (22%) allocated usual care died within 28 days (rate ratio 0.95; 95% CI 0.77-1.16; p=0.60). Interpretation: In patients hospitalised with COVID-19, sotrovimab was associated with reduced mortality in the primary analysis population who had a high serum SARS-CoV-2 antigen concentration at baseline, but not in the overall population. Treatment options for hospitalised patients are limited, and mortality in those receiving current standard care was high. The emergence of high-level resistance to sotrovimab among subsequent SARS-CoV-2 variants limits its current usefulness, but these results indicate that targeted neutralising antibody therapy could potentially still benefit high-risk hospitalised patients in an era of widespread vaccination and Omicron infection.
Kinetics of naturally induced binding and neutralising anti-SARS-CoV-2 antibody levels and potencies among SARS-CoV-2 infected Kenyans with diverse grades of COVID-19 severity: an observational study
Background Given the low levels of coronavirus disease 2019 (COVID-19) vaccine coverage in sub-Saharan Africa (sSA), despite high levels of natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of naturally acquired immunity. Methods We measured whole-spike immunoglobulin G (IgG) and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody-neutralising potency against the wild-type (Wuhan) SARS-CoV-2 pseudovirus in a subset of 51 patients over three successive time points. Binding and neutralising antibody levels and potencies were then tested for correlations with COVID-19 severities. Results Rates of seroconversion increased from day 0 (day of PCR testing) to day 180 (six months) (63.6% to 100 %) and (69.3 % to 97%) for anti-spike-IgG and anti-spike-RBD binding Igs, respectively. Levels of these binding antibodies peaked at day 28 (p<0.01) and were subsequently maintained for six months without significant decay (p>0.99). Similarly, antibody-neutralising potencies peaked at day 28 (p<0.01) but declined by three-fold, six months after COVID-19 diagnosis (p<0.01). Binding antibody levels were highly correlated with neutralising antibody potencies at all the time points analysed (r>0.60, p<0.01). Levels and potencies of binding and neutralising antibodies increased with disease severity. Conclusions Most COVID-19 patients generated SARS-CoV-2 specific binding antibodies that remained stable in the first six months of infection. However, the respective neutralising antibodies decayed three-fold by month-six of COVID-19 diagnosis suggesting that they are short-lived, consistent with what has been observed elsewhere in the world. Thus, regular vaccination boosters are required to sustain the high levels of anti-SARS-CoV-2 naturally acquired neutralising antibody potencies in our population.
Maintenance of high temporal Plasmodium falciparum genetic diversity and complexity of infection in asymptomatic and symptomatic infections in Kilifi, Kenya from 2007 to 2018
Abstract Background High levels of genetic diversity are common characteristics of Plasmodium falciparum parasite populations in high malaria transmission regions. There has been a decline in malaria transmission intensity over 12 years of surveillance in the community in Kilifi, Kenya. This study sought to investigate whether there was a corresponding reduction in P. falciparum genetic diversity, using msp2 as a genetic marker. Methods Blood samples were obtained from children (< 15 years) enrolled into a cohort with active weekly surveillance between 2007 and 2018 in Kilifi, Kenya. Asymptomatic infections were defined during the annual cross-sectional blood survey and the first-febrile malaria episode was detected during the weekly follow-up. Parasite DNA was extracted and successfully genotyped using allele-specific nested polymerase chain reactions for msp2 and capillary electrophoresis fragment analysis. Results Based on cross-sectional surveys conducted in 2007–2018, there was a significant reduction in malaria prevalence (16.2–5.5%: P-value < 0.001), however msp2 genetic diversity remained high. A high heterozygosity index (He) (> 0.95) was observed in both asymptomatic infections and febrile malaria over time. About 281 (68.5%) asymptomatic infections were polyclonal (> 2 variants per infection) compared to 46 (56%) polyclonal first-febrile infections. There was significant difference in complexity of infection (COI) between asymptomatic 2.3 [95% confidence interval (CI) 2.2–2.5] and febrile infections 2.0 (95% CI 1.7–2.3) (P = 0.016). Majority of asymptomatic infections (44.2%) carried mixed alleles (i.e., both FC27 and IC/3D7), while FC27 alleles were more frequent (53.3%) among the first-febrile infections. Conclusions Plasmodium falciparum infections in Kilifi are still highly diverse and polyclonal, despite the reduction in malaria transmission in the community.
The mRNA content of plasma extracellular vesicles provides a window into molecular processes in the brain during cerebral malaria
The impact of cerebral malaria on the transcriptional profiles of cerebral tissues is difficult to study using noninvasive approaches. We isolated plasma extracellular vesicles (EVs) from patients with cerebral malaria and community controls and sequenced their mRNA content. Deconvolution analysis revealed that EVs from cerebral malaria are enriched in transcripts of brain origin. We ordered the patients with cerebral malaria based on their EV-transcriptional profiles from cross-sectionally collected samples and inferred disease trajectory while using healthy community controls as a starting point. We found that neuronal transcripts in plasma EVs decreased with disease trajectory, whereas transcripts from glial, endothelial, and immune cells increased. Disease trajectory correlated positively with severity indicators like death and was associated with increased VEGFA-VEGFR and glutamatergic signaling, as well as platelet and neutrophil activation. These data suggest that brain tissue responses in cerebral malaria can be studied noninvasively using EVs circulating in peripheral blood.