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Sub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency. A systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified. SM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.

Background Due to the relatively low numbers of households in high income countries experiencing food insecurity most studies conflate the levels of severity, which masks between- and within-country differences. This study aims to describe the characteristics of individuals living in high income countries who were moderately or severely food insecure and investigates temporal trends in prevalence. It assesses these characteristics in comparison to those who were food secure. Methods This is a secondary analysis of data collected by the FAO Voices of the Hungry between 2014–2018. The data were collected during the annual Gallup World Polls of nationally representative samples using the Food Insecurity Experience Scale. Data from 34 highly developed, wealthy countries were analysed. The age, gender, income, education, area of residence and household structure of individuals experiencing moderate/severe food insecurity (FI), and severe FI, were compared using ANOVA, Welch’s F, Pearson’s Chi-square, and Linear-by-Linear Association, dependent on the variable of interest. Hierarchical cluster analysis was used to group countries according to their prevalence of moderate/severe FI, and severe FI. Results Overall, 6.5% of the weighted sample were moderately/severely food insecure (M-SFI), while 1.6% were severely food insecure. M-SFI individuals were present in all 34 countries, in all years and across all education levels and income quintiles. The proportion of individuals experiencing moderate/severe FI varied between years and countries. Fifteen countries showed a significant downward temporal trend in prevalence of moderate/severe FI ( p  < 0.001), while three countries demonstrated an increasing temporal trend driven by increasing prevalence in those aged 65 years or less ( p  < 0.001). Comparing individuals experiencing moderate versus severe FI showed over-representation of males, single adult households and lower household income in the severe FI group. Conclusions Individuals across all income, education and age categories living in high income countries are experiencing moderate/severe food insecurity, but with higher prevalence in those experiencing more disadvantage. Over the study period some countries experienced escalating while others demonstrated decreasing moderate/severe FI trends. This comparison of countries with similar economic and human development indices highlights an opportunity to investigate subtle variations in social, economic and education policy that could have profound impacts on food insecurity.

Radical cure of Plasmodium vivax infections is key to the control of vivax malaria. However, the standard doses of 8-aminoquinoline drugs used for radical cure can cause severe haemolysis in G6PD-deficient patients. The availability of near-patient G6PD tests could increase use of primaquine (PQ), however direct evidence of the impacts that G6PD testing has on downstream patient outcomes, such as haemolysis and recurrence is lacking. A linked-evidence model was created to investigate changes in the number of severe haemolysis events and P. vivax recurrences within 6 months of treatment when qualitative G6PD testing was used to guide PQ treatment (0.25mg/kg/day for 14 days and 0.5mg/kg/day for 7 days), compared to prescribing 14-day PQ with no G6PD testing. In the model patients identified as G6PD-deficient received 8-week PQ (0.75mg/kg/week). The model was used to simulate scenarios with 1%, 5% and 10% prevalence of G6PD-deficiency (G6PDd) in theoretical populations of 10,000 male and female P. vivax patients and initially assumed 100% adherence to the prescribed PQ regiment. Results illustrate that G6PD testing to guide the 14-day PQ regiment reduced severe haemolysis by 21-80% and increased recurrences by 3-6%, compared to applying the 14-day PQ regiment without G6PD testing. Results for the 7-day PQ regiment informed by G6PD testing were mixed, dependent on G6PDd prevalence and sex. When adherence to the PQ regiments was less than perfect the model predicted reductions in the number of recurrences at all prevalence levels, provided adherence to 7-day PQ was 5-10% higher than adherence to the 14-day regiment. Introduction of G6PD testing to guide PQ treatment reduces severe haemolysis events for the 14-day regiment, and the 7-day regiment in higher G6PDd prevalence settings, compared to use of 14-day PQ without G6PD testing when all patients adhere to the prescribed PQ treatment. At a population level, there were increases in recurrences, but this could be resolved when the 7-day regiment was used and had superior adherence compared to the 14-day regiment.

Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.

Background. Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Methods. Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Results. Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. Conclusions. These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD). The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone. In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical. A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance. Sensitivity and specificity varied between the LFIs, with specificity found to be significantly higher for whole EDTA blood samples compared to plasma samples in at least 2 LFIs (P≤0.003). Using the altona RT-PCR assay as the bench mark, sensitivities on plasma samples ranged from 79.53% (101/127, 95% CI: 71.46-86.17%) for the DEDIATEST EBOLA (SD Biosensor) to 98.43% (125/127, 95% CI: 94.43-99.81%) for the One step Ebola test (Intec). Specificities ranged from 80.20% (158/197, 95% CI: 74.07-88.60%) for plasma samples using the ReEBOV Antigen test Kit (Corgenix) to 100.00% (98/98, 95% CI: 96.31-100.00%) for whole blood samples using the DEDIATEST EBOLA (SD Biosensor) and SD Ebola Zaire Ag (SD Biosensor). Results also showed the Trombley RT-PCR assay had a lower limit of detection than the altona assay, with some LFIs having higher sensitivity than the altona assay when the Trombley assay was the bench mark. All of the tested EVD LFIs may be considered suitable for use in an outbreak situation (i.e. rule out testing in communities), although they had variable performance characteristics, with none possessing both high sensitivity and specificity. The non-commercial Trombley Zaire ebolavirus RT-PCR assay warrants further investigation, as it appeared more sensitive than the current gold standard, the altona Filovirus Screen RT-PCR assay.

Eritrea was the first African country to complete a nationwide switch in 2016 away from HRP2-based RDTs due to high rates of false-negative RDT results caused by Plasmodium falciparum parasites lacking hrp2/hrp3 genes. A cross-sectional survey was conducted during 2019 enrolling symptomatic malaria patients from nine health facilities across three zones consecutively to investigate the epidemiology of P. falciparum lacking hrp2/3 after the RDT switch. Molecular analyses of 715 samples revealed the overall prevalence of hrp2-, hrp3 -, and dual hrp2/3 -deleted parasites as 9.4% (95%CI 7.4–11.7%), 41.7% (95% CI 38.1–45.3%) and 7.6% (95% CI 5.8–9.7%), respectively. The prevalence of hrp2- and hrp3- deletion is heterogeneous within and between zones: highest in Anseba (27.1% and 57.9%), followed by Gash Barka (6.4% and 37.9%) and Debub zone (5.2% and 43.8%). hrp2/3 -deleted parasites have multiple diverse haplotypes, with many shared or connected among parasites of different hrp2/3 status, indicating mutant parasites have likely evolved from multiple and local parasite genetic backgrounds. The findings show although prevalence of hrp2/3 -deleted parasites is lower 2 years after RDT switching, HRP2-based RDTs remain unsuitable for malaria diagnosis in Eritrea. Continued surveillance of hrp2/3 -deleted parasites in Eritrea and neighbouring countries is required to monitor the trend.

Household food insecurity and inadequate water, sanitation, and hygiene (WASH) contribute to ill health. However, the interactions between household food insecurity, WASH and health have been rarely assessed concurrently. This study investigated compounded impacts of household food insecurity and WASH on self-reported physical and mental health of adults in the Vietnamese Mekong Delta. This cross-sectional survey interviewed 552 households in one northern and one southern province of the Vietnamese Mekong Delta. The survey incorporated previously validated tools such as the Short Form 12-item Health Survey, Household Food Insecurity Assessment Scale, and the Access and Behavioural Outcome Indicators for Water, Sanitation, and Hygiene. Physical and mental health were quantified using the physical health composite score (PCS) and mental health composite score (MCS), respectively. These measures were the dependent variables of interest for this study. Statistical analysis revealed that household food insecurity and using <50 litres of water per person per day (pppd) were independently associated with lower PCS (p<0.05), after adjusting for socio-economic confounders. Household food insecurity and lack of food availability, using <50 litres of water pppd, and the use of untreated drinking water were associated with lower MCS (p<0.05), with water usage being an effect modifier of the relationship between household food insecurity and MCS. The results indicate that being food insecure and having limited potable quality water had a compounding effect on MCS, compared to being individually either food insecure or having limited water. This study is one of only a few that have established a link between potable water availability, food insecurity and poorer physical and mental health. The results also indicate a need to validate national data with fine-scale investigations in less populous regions to evaluate national initiatives with local populations that may be at higher risk. Adopting joint dual-action policies for interventions that simultaneously address water and food insecurity should result in larger improvements in health, particularly mental health, compared to targeting either food or water insecurity in isolation.

Background. Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most using antibodies against Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Reports of P. falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality-assured microscopy. Methods. An agent-based stochastic simulation model of P. falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced, or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Results. Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in >80% of cases, compared with <30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients but no change in the number of antimalarial treatments due to false-negative RDT results. Diagnosis with PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs did not select for PfHRP2-negative parasites. Conclusions. The use of PfHRP2-only RDTs is sufficient to select P. falciparum parasites lacking this protein, thus posing a significant public health problem, which could be moderated by using PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs.

Malaria rapid diagnostic tests (RDTs) can produce false positive (FP) results in patients with human African trypanosomiasis and rheumatoid factor (RF), but specificity against other infectious agents and immunological factors is largely unknown. Low diagnostic specificity caused by cross-reactivity may lead to over-estimates of the number of malaria cases and over-use of antimalarial drugs, at the cost of not diagnosing and treating the true underlying condition. Data from the WHO Malaria RDT Product Testing Programme was analysed to assess FP rates of 221 RDTs against four infectious agents (Chagas, dengue, Leishmaniasis and Schistosomiasis) and four immunological factors (anti-nuclear antibody, human anti-mouse antibody (HAMA), RF and rapid plasma regain). Only RDTs with a FP rate against clean negative samples less than 10% were included. Paired t-tests were used to compare product-specific FP rates on clean negative samples and samples containing non-Plasmodium infectious agents and immunological factors. Forty (18%) RDTs showed no FP results against any tested infectious agent or immunological factor. In the remaining RDTs significant and clinically relevant increases in FP rates were observed for samples containing HAMA and RF (P<0.001). There were significant correlations between product-matched FP rates for RF and HAMA on all RDT test bands (P<0.001), and FP rates for each infectious agent and immunological factor were also correlated between test bands of combination RDTs (P≤0.002). False positive results against non-Plasmodium infectious agents and immunological factors does not appear to be a universal property of malaria RDTs. However, since many malaria RDTs have elevated FP rates against HAMA and RF positive samples practitioners may need to consider the possibility of false positive results for malaria in patients with conditions that stimulate HAMA or RF.