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Investments worth more than £2.7bn are being pledged today in a drive to halve the number of malaria cases across the Commonwealth. Heads of state and business leaders are convening in London to galvanise the fight against the disease, which has seen a resurgence in some areas.
Implementation strategies to improve outcomes in patients with established cardiovascular disease in sub-Saharan Africa: A systematic review.
The protocol was registered in PROSPERO prior to the study implementation (ID: CRD42023465781). The protocol can be accessed at crd.york.ac.uk/PROSPERO/display_record.php?RecordID=465781.
Identification of undetected SARS-CoV-2 infections by clustering of Nucleocapsid antibody trajectories.
During the COVID-19 pandemic, numerous SARS-CoV-2 infections remained undetected. We combined results from routine monthly nose and throat swabs, and self-reported positive swab tests, from a UK household survey, linked to national swab testing programme data from England and Wales, together with Nucleocapsid (N-)antibody trajectories clustered using a longitudinal variation of K-means (N = 185,646) to estimate the number of infections undetected by either approach. Using N-antibody (hypothetical) infections and swab-positivity, we estimated that 7.4% (95%CI: 7.0-7.8%) of all true infections (detected and undetected) were undetected by both approaches, 25.8% (25.5-26.1%) by swab-positivity-only and 28.6% (28.4-28.9%) by trajectory-based N-antibody-classifications-only. Congruence with swab-positivity was respectively much poorer and slightly better with N-antibody classifications based on fixed thresholds or fourfold increases. Using multivariable logistic regression N-antibody seroconversion was more likely as age increased between 30-60 years, in non-white participants, those less (recently/frequently) vaccinated, for lower cycle threshold values in the range above 30, and in symptomatic and Delta (vs. BA.1) infections. Comparing swab-positivity data sources showed that routine monthly swabs were insufficient to detect infections and incorporating national testing programme/self-reported data substantially increased detection. Overall, whilst N-antibody serosurveillance can identify infections undetected by swab-positivity, optimal use requires fourfold-increase-based or trajectory-based analysis.
The Ebola Data Platform: A prospective, standardised, clinical dataset collected during the 2013-2016 West African Ebola outbreak.
The Ebola Data Platform (EDP) was developed to strengthen knowledge and capacity across health, research, and humanitarian communities to reduce the impact of Ebola through responsible data use. This collaborative initiative was established by West African governments, NGOs, academic organisations, and intra-governmental health organisations directly involved in the 2013-2016 West African Ebola outbreak. The platform was established to provide a centralised, standardised dataset of individual patient data collected during the outbreak for the purpose of research to improve Ebola treatment and control, and includes over 13,600 patient records of individuals infected and treated from 22 different Ebola treatment centres across Guinea, Sierra Leone, Liberia, and Nigeria. Patient data are available from treatment centre triage and admission, inpatient clinical observations, and outcomes, with outpatient follow-up available for some datasets. Data include signs and symptoms, pre-existing comorbidities, vital signs, laboratory testing, treatments, complications, dates of admission and discharge, mortality, viral strains, and other data. This publication describes characteristics of the EDP dataset, its architecture, methods for data access and tools for utilising the dataset.
Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART
Background: Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART.Objectives: We report long-term virologic outcomes from a clinical trial.Method: AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST) was a randomised, double-blind, phase II clinical trial. Eligible participants had two consecutive HIV-1 RNA ≥ 1000 copies/mL on first-line ART, mostly tenofovir-emtricitabine-efavirenz. Participants were switched to tenofovir-lamivudine-dolutegravir (TLD) with lead-in 50 mg dolutegravir twice daily in stage one (n = 62), and randomised to TLD with additional lead-in 50 mg dolutegravir or placebo for the first 14 days in stage two (n = 130). We present results up to 158 weeks, combining stages one and two.Results: We enrolled 192 participants: 127/176 (72%) had resistance (Stanford score ≥ 15) to both tenofovir and lamivudine. At week 48, 151/186 (81%; 95% confidence interval [CI] 75%, 87%) had HIV-1 RNA 50 copies/mL. Of 127 participants with follow-up through week 158, 78% (95% CI 70%, 85%) maintained HIV-1 RNA 50 copies/mL, 11% had HIV-1 RNA 50–999 copies/mL, and 11% had HIV-1 RNA ≥ 1000 copies/mL. Twenty-nine participants met criteria for resistance testing: one developed intermediate-level dolutegravir resistance (G118R mutation) at week 96, and one had high-level dolutegravir resistance (E138K, G118R, G163R, T66A mutations) detected at week 146.Conclusion: Among adults switching to TLD with detectable HIV-1 RNA and substantial tenofovir and lamivudine resistance, a high proportion maintained virologic suppression up to 158 weeks. Emergent dolutegravir resistance occurred in ~1% of participants after 2–3 years on second-line TLD.
Disease outbreak data to inform decision-making: the role of disease spread models in the Lao P.D.R. African Swine Fever epidemic, 2019.
Understanding the spread of African Swine Fever (ASF) between villages in the southeast-Asian, low - middle income country context is critical if this high impact disease is to be controlled by good policy and effective field activities in these resource-poor settings. Using governmental reporting data from the 2019 outbreak of ASF in Lao People's Democratic Republic, spatial clustering techniques were used to identify clusters of outbreak villages. Then Approximate Bayesian Computation with Sequential Monte Carlo was used to estimate the transmission parameters of ASF virus between the villages within these clusters. We used a simple disease spread model to understand the impact of parameter estimation on predicted disease spread and thus decision-making. Six clusters of radius 16 to 153km were identified over the 7 month outbreak period. Within these clusters, the basic reproduction number (R0) ranged from 13 to 32 between-villages and whole-village infectious periods ranged from 62 to 68 days. The final model outputs were compared to the original field report data. We found that the ability of the estimated parameters to match field data was heavily reliant on how the original field surveillance data was reported. Specifically, in situations in which cases in a cluster appeared to have been reported as batches (lack of temporal specificity) our modelling approach failed to produce satisfactory outputs in terms of model fit and precision of estimates. This study demonstrates that surveillance for transboundary diseases not only has immediate benefit for disease response, but that good quality surveillance data is valuable for informing future planning for disease response via appropriately parameterised disease spread models. There is a need for ongoing quality control of surveillance and support for field veterinary services to ensure quality data that can be used to drive policy and decision-making.
Applying the Shuffle Model of Differential Privacy to Vector Aggregation
In this work we introduce a new protocol for vector aggregation in the context of the Shuffle Model, a recent model within Differential Privacy (DP). It sits between the Centralized Model, which prioritizes the level of accuracy over the secrecy of the data, and the Local Model, for which an improvement in trust is counteracted by a much higher noise requirement. The Shuffle Model was developed to provide a good balance between these two models through the addition of a shuffling step, which unbinds the users from their data whilst maintaining a moderate noise requirement. We provide a single message protocol for the summation of real vectors in the Shuffle Model, using advanced composition results. Our contribution provides a mechanism to enable private aggregation and analysis across more sophisticated structures such as matrices and higher-dimensional tensors, both of which are reliant on the functionality of the vector case.
Understanding the primary healthcare context in rural South and Southeast Asia: a village profiling study
Abstract Background Understanding contextual factors is critical to the success of health service planning and implementation. However, few contextual data are available at the village level in rural South and Southeast Asia. This study addressed the gap by profiling representative villages across seven sites in Thailand (n=3), Cambodia, Laos, Myanmar and Bangladesh. Methods Key informant surveys supplemented by other information sources were used to collect data from 687 villages on four key indicators (literacy rate, and percentages of attended deliveries, fully immunised children and latrine coverage), as well as access to various services. Data were analysed descriptively. Results Sites varied considerably. Five were highly diverse ethno-culturally and linguistically, and all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. These were generally bypassed by severely ill patients for urban first-level referral hospitals and private sector facilities. While >75% of villages were near primary schools, educational attainment was generally low. Over 70% of villages at each site had mobile phone coverage and availability of electricity was high (≥65% at all sites bar Myanmar). Conclusion These results illustrate the similarities and differences of villages in this region that must be considered in public health research and policymaking.
Operational evaluation of the deployment of Malaria/CRP Duo and Dengue Duo rapid diagnostic tests for the management of febrile illness by village malaria workers in rural Cambodia
Abstract Introduction The decline in malaria cases in Cambodia has led to a relative increase in non-malarial febrile illness. In rural Cambodia, village malaria workers (VMWs) provide early diagnosis and treatment for malaria, but their role and relevance are diminishing as malaria cases decline. Expanding VMW roles would ensure continued utilisation of their services until malaria elimination is achieved and strengthen community health services. Methods A mixed methods operational research study was implemented to evaluate the use of two combination-RDTs (combo-RDTs) as an expansion of the VMW role, enabling VMWs in Cambodia to test for diseases other than malaria for the first time. VMWs in 78 villages in Battambang and Pailin Provinces were trained and provided with either a Malaria/CRP Duo or Dengue Duo RDT to assess febrile patients. Data were collected on VMW consultations, and combo-RDT usage and results. Focus group discussions (FGDs) and competency assessments of combo-RDT usage were conducted with VMWs. The main objectives were to determine whether VMWs could perform these combo-RDTs correctly and follow management algorithms, and whether deployment had an impact on VMW consultation rates. Perspectives concerning role expansion and the feasibility of conducting additional tests were also explored. Results Between June 2022, and May 2023, a total of 2,425 febrile patients were assessed with either a Malaria/CRP Duo or Dengue Duo RDT. Active dengue infection (NS1- and/or IgM-positive) was identified in 1.2% (11/915) of patients. Positive CRP results (> 20 mg/L) were found for 3.2% (48/1,510) of patients. Following deployment, there was an immediate mean increase of 4.4 VMW consultations per month, from 9.0 to 13.4 (p < 0.01). Competency assessments revealed that some VMWs had difficulty performing the Dengue Duo RDT, particularly in collecting the correct blood volume. This limitation may have led to false-negative dengue NS1 results. VMWs and community members were keen to broaden the skills and responsibilities of VMWs. Conclusions Deploying combo-RDTs to VMWs led to a higher utilization of their services. Difficulties performing some aspects of the Dengue Duo RDT, low positivity rates, and a lack of actionable outcomes within the existing context of VMW services suggest that alternative interventions may be better suited for VMW role expansion at this time. Overall, VMWs and community members were receptive to the expansion of the VMW role for a wider range of diseases other than malaria.
The impact of mass screening and treatment interventions on malaria incidence and prevalence: a retrospective analysis of a malaria elimination programme in eastern Myanmar, and systematic review and meta-analysis
Abstract Background Targeted interventions are often needed to accelerate malaria elimination efforts. Mass screening and treatment (MSAT) involves testing all eligible and consenting individuals in an area for malaria and treating all positive individuals simultaneously. However, there are concerns regarding the impact of MSAT. This study evaluates the impact of MSAT on malaria incidence in Karen State, Myanmar, using routine surveillance data, and investigates the impact of MSAT in other settings through a systematic review and meta-analysis. Methods To investigate the impact of MSAT in Karen State, we retrospectively analysed routine malaria surveillance data collected in 10 villages where MSAT was done in 2018. Pre- and post-MSAT malaria incidences were compared, and a negative binomial mixed-effects model was used to estimate the relative change in monthly incidence for each additional year since MSAT. To investigate the impact of MSAT in other settings, we searched Scopus, Ovid MEDLINE, and Web of Science (end date 11th July 2022) for studies assessing the impact of MSAT interventions on the incidence or prevalence of malaria infections. Studies were summarized, and a random-effects meta-analysis was performed on studies grouped according to study design and the comparator used to assess the impact of MSAT. Results In the 10 villages in Karen State, there was an overall reduction in P. falciparum incidence following MSAT (Incidence Rate Ratio 0.37; 95% CI: 0.19, 0.73). However, this is likely due to the ongoing impact of early diagnosis and treatment services offered in these communities, as shown by an overall reduction in incidence in the surrounding area. Results from nine studies identified in the systematic review demonstrate the variable impact of MSAT, which is likely influenced by a variety of factors, including intervention coverage and uptake, baseline malaria endemicity, and methods used for MSAT delivery. Conclusions This retrospective analysis and systemic review highlights the complexities behind the success of targeted interventions for malaria elimination. While these interventions are important drivers for achieving elimination goals, particularly in high-burden settings, it is important that various factors be considered when determining their suitability and how to optimize implementation.
Correction: Evaluating the generalisability of region-naïve machine learning algorithms for the identification of epilepsy in low-resource settings.
[This corrects the article DOI: 10.1371/journal.pdig.0000491.].
Detection of Mycoplasma pneumoniae in hospitalized children with pneumonia in Laos
Mycoplasma pneumoniae has been described worldwide as an important cause of community-acquired pneumonia. From December 2013 to December 2014, 461 children admitted to Mahosot Hospital, Vientiane, Laos, with acute respiratory infection were investigated for upper respiratory microorganisms using probe-based real-time polymerase chain reaction (PCR) (FTD33). M. pneumoniae was detected by FTD33 in the upper respiratory tract of three patients, two girls and one boy, 5.7 and 3.9 years old and 13.6 years old, respectively. They presented with clinical features compatible with M. pneumoniae infection. They improved without M. pneumoniae directed therapy. The two girls were also positive for other potential pathogens. The boy had abnormal pulmonary auscultation, and one of the girls had significant anaemia. These results suggest that enhancement of diagnostic systems for M. pneumoniae detection is needed to improve understanding of the epidemiology of M. pneumoniae infection in Laos.