Malaria Diagnostics Research Articles

Retrospective data analyses of social and environmental determinants of malaria control for elimination prospects in Eritrea

BackgroundThe present study focuses on both long- and short-term malaria transmission in Eritrea and investigates the risk factors. Annual aggregates of information on malaria cases, deaths, diagnostics and control interventions from 2001 to 2008 and monthly reported data from 2009 to 2017 were obtained from the National Malaria Control Programme. We used a generalized linear regression model to examine the associations among total malaria cases, death, insecticide-treated net coverage, indoor residual spraying and climatic parameters.ResultsReduction in malaria mortality is demonstrated by the milestone margins of over 97% by the end of 2017. Malaria incidence likewise declined during the period (from 33 to 5 per 1000 population), representing a reduction of about 86% (R2 = 0.3) slightly less than the decline in mortality. The distribution of insecticide treated nets generally declined between 2001 and 2014 (R2 = 0.16) before increasing from 2015 to 2017, while the number of people protected by indoor residual spraying slightly increased (R2 = 0.27). Higher rainfall was significantly associated with an increased number of malaria cases. The covariates rainfall and temperature are a better pair than IRS and LLIN to predict incidences. On the other hand, IRS and LLIN is a more significant pair to predict mortality cases.ConclusionsWhile Eritrea has made significant progress towards malaria elimination, this progress should be maintained and further improved. Distribution, coverage and utilization of malaria control and elimination tools should be optimized and sustained to safeguard the gains made. Additionally, consistent annual performance evaluation of malaria indicators would ensure a continuous learning process from gains/threats of epidemics and resurgence in regions already earmarked for elimination.

Assessment of the knowledge, attitude and practices of prescribers regarding malaria diagnosis: a cross sectional study among Ghanaian prescribers.

IntroductionMalaria has proven to be the most fatal parasitic disease known to man. Among the pillars to malaria control are early and accurate diagnosis. In 2010, the World Health Organization launched its test, treat and track initiative which seeks to ensure that all suspected cases of malaria are tested. However, after several years of implementation, the use of malaria tests in diagnosing malaria has not been optimum. This study was conducted to assess the level of knowledge of prescribers on malaria Rapid Diagnostic Test and microscopy and to determine factors influencing prescribers' decision to request and use malaria tests in practice.MethodsA cross sectional study was carried out among 100 prescribers of various categories working in 4 hospitals in Ghana in March 2019. A pre-tested self-administered questionnaire was used to collect information on knowledge, malaria diagnostic practices and challenges faced by prescribers regarding parasitological testing for malaria in their health facilities.ResultsOverall, 73% of respondents had good knowledge on malaria diagnostics. Routine use of malaria tests in diagnosing malaria was reported as 84%. Only 9% reported complete reliance on test results. Most participants (90%) reported awareness of the test-based case management of malaria.ConclusionThis study demonstrated that even though there was a high level of awareness of the test-before treatment policy among prescribers, significant numbers did not routinely request a malaria test for all suspected cases of malaria. Factors cited as barriers by prescribers were both health worker and health-system related that are all potentially modifiable.

Improving the Village Health Volunteers’ Knowledge, Malaria Diagnostic Skill and Home Visits through the Observed Training

Municipality of Tidore Islands in North Maluku province, Indonesia, where this study conducted was a malaria endemic area. The malaria Annual Parasite Incidence in this area was 10.8 per 1000 inhabitants in 2010, 8.3 per 1000 inhabitants in 2011, 7.5 per 1000 inhabitants in 2012, 6.11 per 1000 inhabitants in 2013 and 2.10 per 1000 inhabitants in 2014, 2.10 per 1000 inhabitants in 2015. Geographically, this area is consisting of a number of separated islands. This reality reflects the complexity of delivering access, especially health care access to all those separated remote areas. The aim of this study was to increase village health volunteers’ knowledge of malaria and diagnostic skill and home visit through observed training and to analyze the correlation between the knowledge of the village health volunteers toward the diagnostic skill. This research was a Quasi-experimental research based in the community by observing the effects or developments of the results of training interventionscalled “The One Group Pretest-Posttest Design”. A linear regression analysis also conducted to analyze the correlation of observed health volunteer training toward the knowledge and the correlation between knowledge and the diagnostic skill. Result: There has been an increase in village health volunteers’ knowledge after the observed training conducted which included knowledge about malaria in general and the provision of skills to diagnose malaria with sensitivity of 73.4% and specificity of 54.2%Village health volunteers’ knowledge was significantly having correlation toward diagnostic skill (p=0.047) and 90.5% patients that visited completely by village health volunteers taking antimalarial drugs regularly.

Competence of Community Health Workers in conducting Malaria Diagnostic Test for Children Under-Five for Malaria Management in former Northern Bar El Ghazal-South Sudan

Competence of Community Health Workers in conducting Malaria Diagnostic Test for Children Under-Five for Malaria Management in former Northern Bar El Ghazal-South Sudan

False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub-Saharan Africa

Surveillance and diagnosis of Plasmodium falciparum malaria relies predominantly on rapid diagnostic tests (RDT). However, false-negative (FN) RDT results are known to occur for a variety of reasons, including operator...

The XN-30 hematology analyzer for rapid sensitive detection of malaria: a diagnostic accuracy study

BackgroundAccurate and timely diagnosis of malaria is essential for disease management and surveillance. Thin and thick blood smear microscopy and malaria rapid diagnostic tests (RDTs) are standard malaria diagnostics, but both methods have limitations. The novel automated hematology analyzer XN-30 provides standard complete blood counts (CBC) as well as quantification of malaria parasitemia at the price of a CBC. This study assessed the accuracy of XN-30 for malaria detection in a controlled human malaria infection (CHMI) study and a phase 3 diagnostic accuracy study in Burkina Faso.MethodsSixteen healthy, malaria-naive CHMI participants were challenged with five Plasmodium falciparum-infected mosquitoes. Blood was sampled daily for XN-30, blood smear microscopy, and malaria qPCR. The accuracy study included patients aged > 3 months presenting with acute febrile illness. XN-30, microscopy, and rapid diagnostic tests (HRP-2/pLDH) were performed on site; qPCR was done in retrospect. The malaria reference standard was microscopy, and results were corrected for sub-microscopic cases.ResultsAll CHMI participants became parasitemic by qPCR and XN-30 with a strong correlation for parasite density (R2 = 0.91; p < .0001). The XN-30 accurately monitored treatment and allowed detection of recrudescence. Out of 908 patients in the accuracy study, 241 had microscopic malaria (density 24–491,802 parasites/μL). The sensitivity and specificity of XN-30 compared to microscopy were 98.7% and 99.4% (PPV = 98.7%, NPV = 99.4%). Results were corrected for qPCR-confirmed sub-microscopic cases. Three microscopy-confirmed cases were not detected by XN-30. However, XN-30 detected 19/134 (14.2%) qPCR-confirmed cases missed by microscopy. Among qPCR-confirmed cases, XN-30 had a higher sensitivity (70.9% versus 66.4%; p = .0009) and similar specificity (99.6% versus 100%; p = .5) as microscopy. The accuracy of XN-30 for microscopic malaria was equal to or higher than HRP-2 and pLDH RDTs, respectively.ConclusionsThe XN-30 is a novel, automated hematology analyzer that combines standard hemocytometry with rapid, objective, and robust malaria detection and quantification, ensuring prompt treatment of malaria and malaria anemia and follow-up of treatment response.Trial registrationBoth trials were registered on clinicaltrials.gov with respective identifiers NCT02836002 (CHMI trial) and NCT02669823 (diagnostic accuracy study).

Portable Device for Optical Quantification of Hemozoin in Diluted Blood Samples.

This paper focuses on a novel and portable device prototype with optical detectors to quickly and efficiently detect hemozoin (Hz) in blood, aiming at malaria diagnostics. Taking advantage of the particular features of malaria parasite in infected blood, particularly the Hz formation, the main innovation described is a portable device for the optical quantification of parasitic Hz in blood, through optical absorbance spectrophotometry. This device comprises detection chambers for fluidic samples, an optical emission and detection system, and a power supply system to provide autonomy. The working principle is based on colorimetric detection, by absorbance, at six specific wavelengths. A detection algorithm relates the absorbance values at all wavelengths to quantify the Hz concentration, thus working as a biomarker of malaria presence and stage. Under the tested conditions, e.g., in fluidic samples containing synthetic Hz, hemoglobin, and diluted whole blood, the device detected Hz above 1μg/mL concentrations with 100% sensitivity and 96.3% specificity. This paper features an autonomous, portable, 1-min analysis time, and low-cost per test device, without the need for samples, centrifugation, allowing the use of whole blood. The presented device is a step ahead for meeting the growing clinical demands for reliable, rapid, portable, and quantitative malaria diagnosis.

Performance Outcomes from Africa-Based Malaria Diagnostic Competency Assessment Courses.

The U.S. President's Malaria Initiative-funded MalariaCare project implemented an external quality assurance scheme to support malaria diagnostics and case management across a spectrum of health facilities in participating African countries. A component of this program was a 5-day, malaria diagnostic competency assessment (MDCA) course for health facility laboratory staff conducting malaria microscopy. The MDCA course provided a method to quantify participant skill levels in microscopic examination of malaria across three major diagnosis areas: parasite detection, species identification, and parasite quantification. A total of 817 central-, regional-, and peripheral-level microscopists from 45 MDCA courses across nine African countries were included in the analysis. Differences in mean scores with respect to daily marginal performance were positive and statistically significant (P < 0.001) for each challenge type across all participants combined. From pretest to assessment day 4, mean scores for parasite detection, species identification, and parasite quantification increased by 19.1, 34.9, and 38.2 percentage points, respectively. In addition, sensitivity and specificity increased by 20.8 and 13.8 percentage points, respectively, by assessment day 4. Furthermore, the ability of MDCA participants to accurately report Plasmodium falciparum species when present increased from 44.5% at pretest to 67.1% by assessment day 4. The MDCA course rapidly improved the microscopy performance of participants over a short period of time. Because of its rigor, the MDCA course could serve as a mechanism for measuring laboratory staff performance against country-specific minimum competency standards and could easily be adapted to serve as a national certification course.

PO 8475 ENHANCING THE CAPACITY OF THE LIBERIA MEDICINES AND HEALTH PRODUCTS REGULATORY AUTHORITY IN POST-MARKETING SURVEILLANCE OFIN VITRODIAGNOSTICS

BackgroundThe Quality Control Laboratory (QCL) of the Liberia Medicines and Health Products Regulatory Authority (LMHRA) lacks capacity to assess the quality ofin vitrodiagnostics (IVDs). The LMHRA needs be strengthened to develop post-market surveillance (PostMS) regulations in order to fulfil its supervisory role for IVDs used in research and healthcare settings. IGORCADIA, an EDCTP-funded project of LMHRA and the Barcelona Institute for Global Health (ISGlobal) started in December 2017 with the aim of building LMHRA diagnostics assessment capacity.MethodsProject activities targeting the QCL include: the constitution of an in-house Technical Working Group and a Diagnostic Steering Committee involving national stakeholders to develop PostMS regulation; a Training Programme in Diagnostics Research (TPDxR) including a malaria diagnostics performance study as its post-TPDxR exercise.ResultsThe QCL is developing with its new knowledge and networks improved mechanisms to enact its supervisory mandate. QCL staff contributed to the development of guidance for Post-MS. Private sector and government stakeholders helped the LMHRA identify unlicensed premises where IVDs of presumably poor accuracy are available over the counter. Following the TPDxR, the QCL planned quality assurance to oversee the quality assessments on suspected substandard IVDs. Quality control tools, staff training requirements, standard inspection procedures, and PostMS registers and reports were re-designed in accordance with Good Laboratory Practice and guidance from the TPDxR.ConclusionThe LMHRA is strengthening its regulatory, inspection and PostMS capacities thanks to a partnership with a European research institution with expertise in malaria diagnostics development. To ensure that the Liberian population has access to safe quality diagnostics in routine healthcare provision and in future infectious diseases outbreaks, it is of utmost importance that the LMHRA has capacity to assess the accuracy of the non-WHO prequalified IVDs that are currently available outside the healthcare system, and is well-equipped to recall those IVDs identified as substandard.

Comparison of the Accuracy of Four Malaria Diagnostic Methods in a High Transmission Setting in Coastal Cameroon.

Background Despite recommendation from the World Health Organization that all malaria suspected patients undergo a parasitological confirmation using rapid diagnostic test or light microscopy prior to treatment, health facilities in remote malaria endemic settings sometimes resort to presumptive diagnosis of malaria for clinical management for various reasons. Following observation of this practice, we undertook a cross-sectional study aimed at comparing presumptive diagnosis based on axillary temperature, SD Bioline™ rapid test, and light microscopy as strategies for malaria diagnosis in the coastal region of Mutengene in the South West of Cameroon with the overall goal of supporting improved malaria diagnosis at local levels. Methodology Venous blood from 320 participants was used to detect the presence of malaria parasite using SD Bioline™ mRDT and Giemsa stained microscopy or spotted on filter paper for PCR amplification of the 18s rRNA gene of Plasmodium sp following standard procedures. The axillary temperature of each participant was also measured. The sensitivity, specificity, and predictive values and their confidence intervals were determined for each of the methods with PCR as the reference. The area under the curve was used to estimate accuracy of diagnostic method and compared between test method using the X2 test with P<0.05 considered significant. Results The overall diagnostic sensitivities of presumptive diagnosis using axillary temperature, light microscopy, and SD Bioline™ were observed to be 74.30% (95%CI: 67.90-80.01), 94.86% (95%CI: 90.99-97.41), and 95.33% (95%CI: 91.57-97.74), respectively, and their respective diagnostic specificities were 53.77% (95%CI: 43.82-63.51), 94.34% (95%CI: 88.09-97.87), and 94.34%(95%CI: 88.09-97.89). SD Bioline™ had a diagnostic sensitivity of 91.80% [95%CI: 81.90-97.28] at a parasitaemia of less than 500 parasites/μl of blood but a sensitivity of 100% for parasite counts above 500 parasites/μl of blood. The predictive values of the positive test were highly comparable between light microscopy (90.09%, [95%CI: 83.61-94.18]) and SD Bioline™ mRDT (90.91%, [95%CI: 84.50-94.83]), P=0.98 with kappa values of 0.898 but lower for presumptive diagnosis (50.89%, [95%CI: 43.72-58.03]), P<0.0001, and kappa value of 0.277. Perfect agreement was observed between SD Bioline™ mRDT and light microscopy (Cohen kappa= 0.924). Conclusions The study showed that SD Bioline™ was as good as light microscopy in the diagnosis of malaria in remote areas of perennial transmission in South West Cameroon. This study equally revealed the limitations of presumptive diagnosis of malaria (as opposed to the use of RDTs or microscopy). Efforts should be made in such areas to promote parasitological confirmation of malaria using quality assured rapid tests or light microscopy for case management of malaria. The presence of nonnegligible levels of Plasmodium ovale in this study area indicate that treatment guidelines may require revision if same trend is proven in several other areas of same ecology.

Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities

Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure.

Outreach training and supportive supervision for malaria case management in Zambia: the effects of focused capacity building on indicators of diagnostic and clinical performance

BackgroundAccurate diagnosis of malaria and reduced reliance on presumptive treatment are crucial components of quality case management. From 2008 to 2012, the Improving Malaria Diagnostics project, in collaboration with the Zambia National Malaria Control Centre, implemented an external quality assurance scheme partially comprised of outreach training and supportive supervision (OTSS) in an effort to improve malaria case management across a spectrum of health facilities performing laboratory-based malaria diagnostics. OTSS assessments were conducted by project-trained laboratory and clinical supervisors on a regular basis and measured changes in health facility staff performance over time. Standardized supervision tools were used for data collection and guided OTSS teams to assess health facility infrastructure, record keeping practices, stores of supplies and consumables, good laboratory practices, and staff adherence to guidelines for the case management and diagnosis of suspected malaria cases via direct observations or record reviews. The structure of OTSS also allowed supervisors to provide ongoing support to clinicians and laboratory staff through regular mentoring and on-the-job training.ResultsThis analysis included 88 laboratories and 64 clinics each with four repeated supervisory assessments. Over the course of the project there were significant declines in the number of laboratories experiencing stock-outs of microscopy reagents/consumables (p < 0.001) and significant increases in the number of laboratories instituting the use of microscopy positive controls (p < 0.01), conducting parasite counting (p < 0.05), and converting from a semi-quantitative to a quantitative parasite counting methodology (p < 0.001). Performance in malaria diagnostic and clinical practices [i.e. RDT use (mean(diff) = 14.3%, p < 0.001), blood slide preparation (mean(diff) = 14.7%, p < 0.001), blood slide staining and reading (mean(diff) = 14.0%, p < 0.001), fever case management (mean(diff) = 7.3%, p < 0.01)] and prescriber adherence to negative diagnostic test results (mean(diff) = 7.2%, p < 0.05) showed modest, but significant gains from assessment 1 to assessment 4.ConclusionThe external quality assurance scheme provided periodic representations of clinical and laboratory staff performance. OTSS-enrolled health facilities demonstrated improvements to malaria diagnostic skills, adoption of laboratory best practices, strengthened fever case management practices, and improved prescriber adherence to negative malaria test results.

Results analysis of Jiangsu Provincial Malaria Diagnostic Reference Laboratory in 2017

To analyze the results of samples testing of Jiangsu Provincial Malaria Diagnostic Reference Laboratory in 2017, so as to provide the evidence for improving the malaria diagnostic performance in this province. The samples of reported malaria cases in Jiangsu were collected by the provincial reference laboratory (PRL) in 2017. The microscopy and nucleic acid test were performed to confirm the infection of Plasmodium species of each case, while Plasmodium antigen tests (rapid diagnostic test, RDT) were performed as well. The detection results were analyzed among different areas and different species. Totally 242 malaria cases were reported and the samples were collected by PRL in 2017. A total of 239 cases were confirmed Plasmodium infections, including 163 cases of Plasmodium falciparum infection, 21 cases of P. vivax infection, 11 cases of P. malariae infection, 43 cases of P. ovale infection, and 1 case of P. falciparum and P. ovale mixed-infection. The diagnostic coincidence rates of reported malaria case in 13 prefectures with districts were all > 80%, and the total coincidence rate was 88.8%. The species diagnostic coincidence rates of P. falciparum, P. vivax, P. malariae, and P. ovale were 98.8%, 57.1%, 63.6%, and 81.4% respectively, and the detection rates by RDT to those four species infections were 95.7%, 85.0%, 63.6% and 79.1% respectively. In 2017, the malaria diagnostic quality of medical technicians is generally high in Jiangsu Province. However, the diagnostic capacity is slightly different among different regions, and the ability to identify non- P. falciparum parasites remains to be improved. RDT is not ideal for the detection of non-P. falciparum infection. In the current stage of malaria elimination, the malaria diagnostic capacity of technicians in all the sectors should be strengthened and maintained.

Imaging & identification of malaria parasites using cellphone microscope with a ball lens.

We have optimized the design and imaging procedures, to clearly resolve the malaria parasite in Giemsa-stained thin blood smears, using simple low-cost cellphone-based microscopy with oil immersion. The microscope uses a glass ball as the objective and the phone camera as the tube lens. Our optimization includes the optimal choice of the ball lens diameter, the size and the position of the aperture diaphragm, and proper application of immersion, to achieve diagnostic capacity in a wide field of view. The resulting system is potentially applicable to low-cost in-the-field optical diagnostics of malaria as it clearly resolves micron-sized features and allows for analysis of parasite morphology in the field of 50 × 50 μm, and parasite detection in the field of at least 150 × 150 μm.

Improving prompt access to malaria diagnostics and treatment in rural remote areas using financial benefit for community health workers in Kilosa district, Tanzania.

PurposeImproving access to malaria treatment in rural remote areas remains a major challenge facing innovative strategies, such as Accredited Drug Dispensing Outlets (ADDOs) and Community Health Workers (CHWs) programs in Tanzania. This study tested the effectiveness of a financial benefit approach to motivate CHWs to improve prompt access to malaria treatment.Patients and methodsWe applied a quasi-experimental study design in rural-remote areas in Kilosa district, Tanzania. Febrile children in selected intervention areas were provided access to malaria diagnostic and treatment at a minimal fee to CHWs and compared with non-intervention areas. We measured impact using difference in differences (DID) analysis.ResultsAt baseline, 870 children <5 years of age were recruited and 1,127 in post-intervention. The DID in prompt access to malaria diagnostics and treatment was 28.0% in favor of intervention. A net pre and post decrease (DID=24.1%) in seeking care from public facilities was observed, signifying decrease in workload. Incidentally, knowledge on malaria treatment increased in intervention area (DID 11%–21%).ConclusionUsing the financial benefit approach, CHWs were able to significantly improve prompt access to malaria diagnostics and treatment in rural remote areas. Scaling up of the strategy might speed up the pace toward achieving national target of accurate diagnosis and appropriate treatment by 80% in 2020.

Multiplex real-time PCR for diagnosing malaria in a non-endemic setting: a prospective comparison to conventional methods

Almost a decade ago our diagnostic laboratory implemented an in-house real-time PCR for the detection of Plasmodium DNA to diagnose malaria in parallel with conventional diagnostics, i.e., microscopy (thick and thin smears), quantitative buffy coat microscopy (QBC), and a rapid diagnostic test (RDT). Here we report our experiences and make a comparison between the different diagnostic procedures used in this non-endemic setting. All patients during the period February 2009–December 2017 suspected of malaria were prospectively tested at the moment of sample collection. Both PCR and conventional malaria diagnostics were carried out on a total of 839 specimens from 825 patients. In addition, three Plasmodium falciparum (Pf) patients were closely followed by real-time PCR and microscopy after treatment. Overall, 56 samples (55 patients) tested positive by real-time PCR, of which six were missed by microscopy and seven by QBC. RDT showed fairly good results in detecting Pf, whereas specificity was not optimal. RDT failed to detect 10 of 17 non-Pf PCR positive specimens. One Plasmodium malariae patient would have been missed if only conventional diagnostic tests had been used. The high sensitivity of the PCR was confirmed by the number of PCR positive, microscopy negative post-treatment samples. In conclusion, within our routine diagnostic setting, malaria real-time PCR not only showed a high level of agreement with the conventional methods used, but also showed higher sensitivity and better specificity. Still, for complete replacement of the conventional procedures in a non-endemic setting, the time-to-results of the real-time PCR is currently too long.

The XN-30 Haematology Analyser for Rapid Sensitive Detection of Malaria: A Diagnostic Accuracy Study

Background: Accurate and timely diagnosis of malaria is essential for disease management and surveillance. Microscopy and malaria rapid diagnostic tests (RDTs) are standard malaria diagnostics, but both methods have significant limitations. The novel automated haematology analyser XN-30 provides standard complete blood counts (CBC) as well as quantification of malaria parasitaemia at the price of an RDT. This study assessed the accuracy of XN-30 for malaria detection in a Controlled Human Malaria Infection (CHMI) study and subsequently in a phase-3 diagnostic accuracy study in Burkina Faso. Methods: Sixteen healthy malaria-naive CHMI participants were challenged according to standardized protocols by exposure to five laboratory reared Plasmodium falciparum-infected mosquitoes and sampled daily for XN-30, blood smear microscopy, RDT and qPCR analyses (NCT02836002). The blinded diagnostic accuracy study included 908 patients aged >3 months, presenting with acute febrile illness (NCT02669823). XN-30, microscopy and RDTs (HRP-2/pLDH) were performed on site, qPCR was done in retrospect. Microscopy was used as reference standard, results were corrected for qPCR confirmed submicroscopic cases. RDT results were compared to XN-30 for both microscopic and qPCR confirmed cases. Findings: All CHMI participants became parasitaemic by qPCR and XN-30 with a strong correlation for parasite density (R2=0·91). In the field study, the sensitivity and specificity of XN-30 compared to microscopy were 98.7% and 99.4% respectively (PPV 98·7%, NPV 99·4%, AUC=0·99). Three microscopy confirmed cases were not detected by XN-30. However, XN-30 detected 24 of 119 (20.2%) qPCR confirmed submicroscopic cases. The sensitivity and specificity of XN-30 to diagnose microscopic cases were higher than that of HRP-2 and pLDH RDTs. Interpretation: XN-30 is a novel rapid automated malaria diagnostic outperforming standard microscopy and RDT's at a similar price. Since it simultaneously provides haemocytometric data and allows high-throughput testing, XN-30 is an attractive diagnostic tool for malaria management and control. Funding Statement: The CHMI study was funded by PATH MVI. Sysmex Corporation provided the analyzer and reagents. The diagnostic accuracy study was funded by Sysmex Corporation. The funding sources were involved in the study design, but not in data collection, analysis and interpretation, or the preparation of the report. Declaration of Interests: AvV and QdM have a non-restricted research grant from SYSMEX, which funded the current study. None of the other authors had any conflict of interest. Ethics Approval Statement: The studies were performed in accordance with the declaration of Helsinki and GCLP guidelines. The CHMI study was approved by the central committee for research involving human subjects (CCMO) of the Netherlands (NL56659.091.16), and the Western Institutional Review Board (WIRB) in the USA. The diagnostic study was approved by the national ethical committee of Burkina Faso (ref 2015-01-006), the internal review board of IRSS (ref A03-2016/CEIRES) the ethical committee of the university hospital of Antwerp (ref 15/47/492) and the institutional review board of the Institute of Tropical Medicine Antwerp (ref 1029/15).

Use of Capillary Blood Samples Leads to Higher Parasitemia Estimates and Higher Diagnostic Sensitivity of Microscopic and Molecular Diagnostics of Malaria Than Venous Blood Samples.

Diagnosis of malaria is usually based on samples of peripheral blood. However, it is unclear whether capillary (CAP) or venous (VEN) blood samples provide better diagnostic performance. Quantitative differences of parasitemia between CAP and VEN blood and diagnostic performance characteristics were investigated. Patients were recruited between September 2015 and February 2016 in Gabon. Light microscopy and quantitative polymerase chain reaction (qPCR) measured parasitemia of paired CAP and VEN samples. CAP and VEN performance characteristics using microscopy were evaluated against a qPCR gold standard. Microscopy revealed a median parasitemia of 495/μL in CAP and 429/μL in VEN samples, manifesting in a 16.6% (P = .04) higher CAP parasitemia compared with VEN parasitemia. Concordantly, in qPCR -0.278 (P = .006) cycles were required for signal detection in CAP samples. CAP sensitivity of microscopy relative to the gold standard was 81.5% vs VEN sensitivity of 73.4%, while specificities were 91%. CAP and VEN sensitivities dropped to 63.3% and 45.9%, respectively, for a subpopulation of low-level parasitemias, whereas specificities were 92%. CAP sampling leads to higher parasitemias compared to VEN sampling and improves diagnostic sensitivity. These findings may have important implications for routine diagnostics, research, and elimination campaigns of malaria.

Use of a public-private partnership in malaria elimination efforts in Sri Lanka; a case study

BackgroundIn special circumstances, establishing public private partnerships for malaria elimination may achieve targets faster than the state sector acting by itself. Following the end of the separatist war in Sri Lanka in 2009, the Anti Malaria Campaign (AMC) of Sri Lanka intensified malaria surveillance jointly with a private sector partner, Tropical and Environmental Diseases and Health Associates Private Limited (TEDHA) with a view to achieving malaria elimination targets by 2014.MethodsThis is a case study on how public private partnerships can be effectively utilized to achieve malaria elimination goals. TEDHA established 50 Malaria Diagnostic Laboratories and 17 entomology surveillance sentinel sites in consultation with the AMC in areas difficult to access by government officials (five districts in two provinces affected by war).ResultsTEDHA screened 994,448 individuals for malaria, of which 243,867 were screened at mobile malaria clinics as compared to 1,102,054 screened by the AMC. Nine malaria positives were diagnosed by TEDHA, while the AMC diagnosed 103 malaria cases in the same districts in parallel. Over 13,000 entomological activity days were completed. Relevant information was shared with AMC and the data recorded in the health information system.ConclusionsA successful public-private partnership model for malaria elimination was initiated at a time when the health system was in disarray in war ravaged areas of Sri Lanka. This ensured a high annual blood examination rate and screening of vulnerable people in receptive areas. These were important for certification of malaria-free status which Sri Lanka eventually received in 2016.

The comparison of detection methods of asymptomatic malaria in hypoendemic areas

Malaria is still a problem that disrupts public health in North Sumatera. Late diagnosis will increase the chances of increased morbidity and mortality due to malaria. The early detection of asymptomatic malaria is one of the best efforts to reduce the transmission of the disease. Early detection is certainly must be done on suspect patients who have no malaria complaints. Passive Case Detection (PCD) methods seem hard to find asymptomatic malaria. This study was conducted to compare ACD (Active Case Detection) and PCD methods in asymptomatic malaria detection in the hypoendemic areas of malaria. ACD method is done by going to the sample based on secondary data. Meanwhile, PCD is done on samples that come to health services. Samples were taken randomly and diagnosis was confirmed by microscopic examination with 3% Giemsa staining, as gold standard of malaria diagnostics. There was a significant difference between ACD and PCD detection methods (p = 0.034), where ACD method was seen superior in detecting malaria patients in all categories, such as: clinical malaria (65.2%), asymptomatic malaria (65.1%) and submicroscopic malaria (58.5%). ACD detection methods are superior in detecting malaria sufferers, especially asymptomatic malaria sufferers.