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Global efforts to fight malaria have hit a plateau and new tools are needed to achieve global goals. In this context, a consortium led by the Barcelona Institute for Global Health was awarded $25.3m from Unitaid (unitaid.org) to evaluate mass drug administration of ivermectin to humans and livestock in Tanzania and Mozambique, to kill the mosquitoes that transmit malaria. KWTRP Marta Maia will contribute as lead entomologist to BOHEMIA.
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Credit: Laura Delgado / ISGlobal
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.
Defining the noma research agenda.
• A 1-day symposium brought together over 100 individuals with lived experience of noma, expertise in neglected tropical diseases, and public health, including researchers, health advocates, and clinicians. The involvement of noma survivors was invaluable and added an important perspective in defining the research agenda. • The most pressing research needs identified were: ○ Clear case definition of noma ○ Early case detection and robust surveillance ○ Psychosocial and economic impact of noma ○ Decision support for diagnosing acute necrotizing gingivitis and associated antibiotic regimen(s) with treatment duration ○ Deeper understanding of risk factors and social determinants ○ Identification of effective information, education, and communication strategies ○ Effectiveness of surgical services ○ Testing decentralized follow-up for patients • An important conclusion was that noma research and control activities must be integrated across sectors and disciplines, such as neglected tropical diseases, oral health, nutrition, and child health programs including immunization.
Safety and efficacy of single-dose primaquine to interrupt Plasmodium falciparum malaria transmission in children compared with adults: a systematic review and individual patient data meta-analysis.
BackgroundAdding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. We aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged ≥15 years), and between low and moderate-to-high transmission areas.MethodsFor this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. We included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (≤0·75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. We quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy).FindingsOf 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19·3%) young children (aged <5 years), 2827 (46·7%) older children (aged 5 years to <15 years), and 2058 (34·0%) adults (aged ≥15 years). Adding a single low dose of primaquine (0·2-0·25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0·34, 95% CI 0·22-0·52; p<0·001) and infectivity to mosquitoes over time (aOR per day 0·02, 0·01-0·07, p<0·001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1·08, 0·52-2·23; p=0·84) and adults (0·50, 0·20-1·25; p=0·14) and between low-transmission and moderate-to-high transmission settings (1·07, 0·46-2·52; p=0·86), and on infectivity to mosquitoes in young children compared with older children (1·36, 0·07-27·71; p=0·84) and adults (0·31, 0·01-8·84; p=0·50) and between low-transmission and moderate-to-high transmission settings (0·18, 0·01-2·95; p=0·23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0·25 mg/kg (1·56, 0·65-3·79; p=0·32 at day 7). However, patients given a primaquine dose of less than 0·2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5·68, 1·38-23·48; p=0·016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0·25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children.InterpretationRegardless of malaria transmission intensity and age group, a single dose of 0·25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance.FundingThe EU and the Bill & Melinda Gates Foundation.
Influence of context on engagement with COVID-19 testing: a scoping review of barriers and facilitators to testing for healthcare workers, care homes and schools in the UK
ObjectiveThe UK government’s response to the COVID-19 pandemic included a ‘test, trace and isolate’ strategy. Testing services for healthcare workers, care homes and schools accounted for the greatest spend and volume of tests. We reviewed relevant literature to identify common and unique barriers and facilitators to engaging with each of these testing services.DesignScoping review.Search strategyPubMed, Scopus and the WHO COVID-19 Research Database were searched for evidence published between 1 January 2020 and 7 November 2022. This was supplemented by evidence identified via free-text searches on Google Scholar and provided by the UK Health Security Agency (UKHSA).Data extraction and synthesisData were extracted by a team of reviewers and synthesised thematically under the broad headings of perceptions, experiences, barriers and facilitators to engaging with the COVID-19 testing programme.ResultsThis study included 40 sources, including 17 from projects that informed UKHSA’s decisions during the pandemic. Eight themes emerged and were used to categorise barriers and facilitators to engaging with the testing services for healthcare workers, care homes and schools: (1) perceived value, (2) trust in the tests and public bodies, (3) importance of infrastructure, (4) impact of media and social networks, (5) physical burden of the test, (6) perceived capability to undertake testing, (7) importance of relevant information and 8) consequences of testing.ConclusionsUniversal barriers and facilitators to engagement with the testing programme related to the core elements of each testing service, such as uncomfortable specimen collection and the influence of media and peers; these could be mitigated or leveraged to increase engagement across settings. However, the individuals involved, perceptions of value and available resources differed across services, leading to unique experiences between settings. Thus, consideration of context is crucial when designing and implementing a testing programme in response to a pandemic.
Malaria morbidity, mortality and associated costs in Indonesia: analysis of the National Health Insurance claim dataset.
INTRODUCTION: Data on morbidity, mortality and cost for malaria-related hospitalisation are important for prioritising resources for malaria control strategies, but these data are often limited. The aim of this study was to understand the current malaria service delivery in Indonesia, including referral rates to hospitals, mortality outcomes and malaria-related costs at hospitals, using data from National Health Insurance claims. METHODS: Data were gathered from the recent Indonesian National Health Insurance dataset for claims made between 2015 and 2020. Cases were selected for any diagnosis with the international classification of diseases-10th revision codes for malaria-related diseases. Patients' sociodemographic status, repeated presentations to healthcare facilities, referral patterns and costs of treatment for the hospital settings were assessed by malaria species. Costs were reported in 2020 US$. RESULTS: Data were available for 12 970 episodes of malaria, which occurred in 8833 patients. Plasmodium falciparum accounted for 6019 (46.4%) episodes, and P. vivax for 4307 (33.2%) episodes. The incidence rates were 0.38 (95% CI 0.29 to 0.47) per person-years for P. falciparum and 0.33 (95% CI 0.19 to 0.52) for P. vivax. 46% of malaria cases initially presented at the hospital. Among these patients, the mean cost was US$16.2 (SD 4.4) for an outpatient consultation and US$228.7 (SD 122.6) for inpatient care. In total, 4.8% (623) of patients re-presented to the hospital within 30 days of a malaria episode, of whom 1.7% (219) required admission for inpatient care, which was estimated to cost US$230.0 (SD 105.5). The risk of mortality for inpatients with P. falciparum malaria was 2.1% (36/1718) compared with 1.2% (16/1359) for patients with P. vivax malaria; p=0.069. CONCLUSIONS: The National Health Insurance claim data provide detailed costing estimates. Integrating data from the existing malaria information system with the data from the National Health Insurance claims can provide important insights into the healthcare costs associated with the management of malaria that could help optimise national antimalarial policy.
Temporal correlations between RBD-ACE2 blocking and binding antibodies to SARS-CoV-2 variants in CoronaVac-vaccinated individuals and their persistence in COVID-19 patients.
Antibodies play a crucial role in protection against SARS-CoV-2. Understanding the correlation between binding and functional antibodies is essential to determine whether binding antibody levels can reliably predict neutralizing activity. We assessed antibody responses in 111 individuals vaccinated with the inactivated vaccine CoronaVac and 111 COVID-19 patients in Thailand. Plasma levels of ACE2-blocking antibodies targeting the receptor-binding domain (RBD) of SARS-Co-V2 variants were measured before vaccination and at 14 and 28 days after the second dose using a multiplex surrogate virus neutralization test. Anti-spike and anti-nucleocapsid antibodies were quantified by electrochemiluminescence immunoassay, and anti-RBD IgG by ELISA. After vaccination, blocking, anti-spike, and IgG antibody levels increased but declined rapidly within a month, whereas antibody levels in COVID-19 patients increased and persisted. Blocking and anti-spike antibody correlated at day 14 post-vaccination but not at day 28. In COVID-19 patients, correlations were moderate at day 14, and stronger at day 28. Correlations were weaker for Omicron subvariants than for the ancestral strain and non-Omicron variants. The weak correlation between blocking and anti-RBD IgG suggests binding antibodies might not predict neutralizing activity. These findings highlight the temporal nature of CoronaVac-induced immunity and the need for booster doses and variant-adapted vaccine.
Metformin as adjunctive therapy in overweight and obese patients with dengue: trial data
Trial dataset supporting publications.