Positive Rapid Diagnostic Test Result Research Articles

Field evaluation of validity and feasibility of Pan-Lassa rapid diagnostic test for Lassa fever in Abakaliki, Nigeria: a prospective diagnostic accuracy study.

Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria. We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity. Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read. The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings. Médecins Sans Frontières.

Correlation Of Positive IgM or IgG RDT (Rapid Diagnostic Test) Results with CRP (C-Reactive Protein) Levels in Dengue Hemorrhagic Fever Patients

Background: Laboratory diagnosis of Dengue Hemorrhagic Fever includes the IgM & IgG RDT (Rapid Diagnostic Test) examination which differentiates primary and secondary dengue infection. The presence of inflammation in the body caused by the dengue virus needs to be examined for C-Reactive Protein. Methods: This research is an analytical observational study with a cross sectional approach. Thesample used is a plasma sample of a patient diagnosed with DHF with a positive IgM or IgG RDT result. Results: Positive IgM RDT results were 6 people (17%) and positive IgG were 30 people (83%). The results of a qualitative CRP study were 24 people (67%) with positive CRP levels. Semi-quantitative CRP average level for positive IgG was29.33. The results of the Spearman's Rank statistical test obtained a value of p = 0.003 <0.05 which showed a significant result. Conclusion:Clinically it shows that the more positive IgM or IgG RDT results obtained, the higher the CRP level which indicates the severity/inflammation that is formed in the body.

Glucose-6-Phosphate Dehydrogenase (G6PD) Measurement Using Biosensors by Community-Based Village Malaria Workers and Hospital Laboratory Staff in Cambodia: A Quantitative Study.

Vivax malaria can relapse after an initial infection due to dormant liver stages of the parasite. Radical cure can prevent relapses but requires the measurement of glucose-6-phosphate dehydrogenase enzyme (G6PD) activity to identify G6PD-deficient patients at risk of drug-induced haemolysis. In the absence of reliable G6PD testing, vivax patients are denied radical curative treatment in many places, including rural Cambodia. A novel Biosensor, 'G6PD Standard' (SD Biosensor, Republic of Korea; Biosensor), can measure G6PD activity at the point of care. The objectives of this study were to compare the G6PD activity readings using Biosensors by village malaria workers (VMWs) and hospital-based laboratory technicians (LTs), and to compare the G6PD deficiency categorization recommended by the Biosensor manufacturer with categories derived from a locally estimated adjusted male median (AMM) in Kravanh district, Cambodia. Participants were enrolled between 2021 and 2022 in western Cambodia. Each of the 28 VMWs and 5 LTs received a Biosensor and standardized training on its use. The G6PD activities of febrile patients identified in the community were measured by VMWs; in a subset, a second reading was done by LTs. All participants were tested for malaria by rapid diagnostic test (RDT). The adjusted male median (AMM) was calculated from all RDT-negative participants and defined as 100% G6PD activity. VMWs measured activities in 1344 participants. Of that total, 1327 (98.7%) readings were included in the analysis, and 68 of these had a positive RDT result. We calculated 100% activity as 6.4 U/gHb (interquartile range: 4.5 to 7.8); 9.9% (124/1259) of RDT-negative participants had G6PD activities below 30%, 15.2% (191/1259) had activities between 30% and 70%, and 75.0% (944/1259) had activities greater than 70%. Repeat measurements among 114 participants showed a significant correlation of G6PD readings (rs = 0.784, p < 0.001) between VMWs and LTs. Based on the manufacturer's recommendations, 285 participants (21.5%) had less than 30% activity; however, based on the AMM, 132 participants (10.0%) had less than 30% activity. The G6PD measurements by VMWs and LTs were similar. With the provisions of training, supervision, and monitoring, VMWs could play an important role in the management of vivax malaria, which is critical for the rapid elimination of malaria regionally. Definitions of deficiency based on the manufacturer's recommendations and the population-specific AMM differed significantly, which may warrant revision of these recommendations.

313. Performance of Rapid Diagnostic Testing at Days 4-6 from Diagnosis: Implications for Discharge from Isolation on a University Campus

Abstract Background Omicron rapidly replaced delta as the predominant strain causing COVID-19 related illness in the United States (US) in December 2021, the same month the US CDC reduced the recommended isolation period from 10 to 5 days for asymptomatic individuals or those with resolving symptoms. New evidence suggests some asymptomatic individuals with omicron remain culture positive beyond 5 days from diagnosis. We sought to evaluate the performance of a SARS-CoV-2 antigen rapid diagnostic test (RDT) in predicting persistent potential for transmission at the end of a five-day isolation period among young, fully vaccinated individuals in a university community setting. Methods A subgroup of participants enrolled in a longitudinal COVID-19 cohort were asked to self-perform RDTs on days 4 to 6 from diagnostic test date in addition to a separate self-collected anterior nasal swab used for culture and RT-PCR, and a daily symptom screen (15 COVID-19 symptom questions on a 4-point scale). We calculated the daily and overall sensitivity and specificity of the RDTs in comparison to SARS-CoV-2 culture result. We also compared the N1 cycle threshold (CT) values and symptom score on each day of the study by RDT results. Results Of 23 participants, the mean age was 20 years, all had completed their primary COVID-19 vaccine series, and 13 (65.0%) had received a booster vaccine (Table 1). Compared to culture, sensitivity and specificity of the RDTs were 100% and 62% respectively (Table 2). Compared to participants with negative RDTs, median CT values were lower in those with positive RDTs on each day of the study (Figure 1). Participants who had positive RDTs on all three days had higher symptom scores (Figure 2) than those without. Conclusion RDTs have a high sensitivity in detecting culture positive SARS-CoV-2 on Days 4 to 6 from initial diagnostic test. However, the high false positive rate of 38% means that over a third of culture negative individuals will stay in isolation longer than necessary if RDTs are used in test to release from isolation protocols. Viral loads (CT values) and symptom scores were higher for participants with persistently positive RDT result. An approach that uses a combination of RDTs, CT values and symptom score may prove useful in guiding isolation duration. Disclosures Davidson H. Hamer, MD, Trinity Biotech: Advisor/Consultant Catherine M. Klapperich, Ph.D., BioSens8, LLC: Ownership Interest.

Experience and confidence in health technologies: evidence from malaria testing and treatment in Western Kenya

BackgroundLow adoption of effective health technologies increases illness morbidity and mortality worldwide. In the case of malaria, effective tools such as malaria rapid diagnostic tests (RDTs) and artemisinin-combination therapies (ACTs) are both under-used and used inappropriately. Individuals’ confidence in RDTs and ACTs likely affects the uptake of these tools.MethodsIn a cohort of 36 households (280 individuals) in Western Kenya observed for 30 months starting in June 2017, we examined if experience with RDTs and ACTs changes people’s beliefs about these technologies and how those beliefs affect treatment behavior. Household members requested a free RDT from the study team any time they suspected a malaria illness, and positive RDT results were treated with a free ACT. We conducted annual, monthly, and sick visit surveys to elicit beliefs about the accuracy of malaria RDT results and the effectiveness of ACTs. Beliefs were elicited on a 5-point Likert scale from “very unlikely” to “very likely.”ResultsOver the study period, the percentage of survey respondents that said a hypothetical negative RDT result was “very likely” to be correct increased from approximately 55% to 75%. Controlling for initial beliefs, people who had been tested at least once with an RDT in the past year had 3.6 times higher odds (95% CI [1 1.718 7.679], P = 0.001) of saying a negative RDT was “very likely” to be correct. Confidence in testing was associated with treatment behavior: those who believed a negative RDT was “very likely” to be correct had 1.78 times higher odds (95% CI [1.079 2.934], P = 0.024) of adhering to a negative RDT result (by not taking ACTs) than those who were less certain about the accuracy of negative RDTs. Adherence to a negative test also affected subsequent beliefs: controlling for prior beliefs, those who had adhered to their previous test result had approximately twice the odds (OR = 2.19, 95% CI [1.661 2.904], P < 0.001) of saying that a hypothetical negative RDT was “very likely” to be correct compared to those who had not adhered.ConclusionsOur results suggest that greater experience with RDTs can not only increase people’s confidence in their accuracy but also improve adherence to the test result.

Assessment of CareStart G6PD rapid diagnostic test and CareStart G6PD biosensor in Mauritania

BackgroundThe elimination of Plasmodium vivax malaria requires 8-aminoquinolines, which are contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of acute haemolytic anaemia. Several point-of-care devices have been developed to detect G6PD deficiency. The objective of the present study was to evaluate the performance of two of these devices against G6PD genotypes in Mauritania.MethodsOutpatients were screened for G6PD deficiency using CareStart™ rapid diagnostic test (RDT) and CareStart™ G6PD biosensor in Nouakchott, Mauritania, in 2019–2020. African-type and Mediterranean-type G6PD genotypes commonly observed in Africa were determined by polymerase chain reaction-restriction fragment length polymorphism and sequencing. Qualitative variables were compared using Fisher’s exact test.ResultsOf 323 patients (74 males and 249 females), 5 males and 2 homozygous females had the African-type A- genotype: A−(202) in 3 males and 2 females and G6PD A−(968) in 2 males. Among heterozygous females, 13 carried G6PD A−(202), 12 G6PD A−(968), and 3 G6PD A−(542) variants. None had the Mediterranean-type G6PD genotype. Eight had a positive G6PD RDT result, including all 7 hemizygous males and homozygous females with A- or A-A- (0.12 to 2.34 IU/g haemoglobin, according to G6PD biosensor), but RDT performed poorly (sensitivity, 11.1% at the cut-off level of < 30%) and yielded many false negative tests. Thirty-seven (50.0%) males and 141 (56.6%) females were anaemic. The adjusted median values of G6PD activity were 5.72 and 5.34 IU/g haemoglobin in non-anaemic males (n = 35) and non-anaemic males and females (n = 130) with normal G6PD genotypes using G6PD biosensor, respectively. Based on the adjusted median of 5.34 IU/g haemoglobin, the performance of G6PD biosensor against genotyping was as follows: at 30% cut-off, the sensitivity and specificity were 85.7% and 91.7%, respectively, and at 80% cut-off, the sensitivity was 100% while the specificity was 64.9%.ConclusionsAlthough this pilot study supports the utility of biosensor to screen for G6PD deficiency in patients, further investigation in parallel with spectrophotometry is required to promote and validate a more extensive use of this point-of-care device in areas where P. vivax is highly prevalent in Mauritania.Graphic abstract

Investigation of HRPF2 Gene Deletion in Plasmodium Falciparum in Northwestern Nigeria

Abstract Malaria Rapid Diagnostic Tests (RDTs) plays an important role in malaria management and control. The Pf HRP2 based RDT kit is the most widely used RDT for malaria diagnosis in Nigeria but is affected by the deletion of HRP2 gene in Plasmodium falciparum parasites. Therefore, identifying the prevalence and distribution of Plasmodium falciparum parasites with deleted Pf HRP2 is important for malaria control. Pf HRP2 gene deletion was assessed in this study by first carrying out Giemsa stained thick blood film microscopy and Pf HRP2 RDT strip test. The samples were further analyzed for molecular examination by PCR assay for multiple single–copy genes (Pf Cox3, Pf HRP2, Pf HRP3 and Pf Beta tubulin). This study found the existence of eight (8) Plasmodium falciparum isolates lacking the HRP2 gene in the samples analyzed, this necessitates the need to develop a unique RDT Kit targeting other housekeeping genes unique for Plasmodium falciparum with far greater sensitivity than the current ones as to reduce the chances of false negative RDT result as well as developing unique RDT Kits targeting both PfHRP2 and PfHRP3 genes concomitantly in order to reduce the chances of having a false positive RDT results.

Predictive Performance of Rapid Diagnostic Tests for Falciparum Malaria and Its Modeled Impact on Integrated Community Case Management of Malaria in Sub-Saharan African Febrile Children.

BackgroundIntegrated community case management (iCCM) of malaria complements public health services to improve access to timely diagnosis and treatment of malaria. ICCM relies on standardized test-and-treat algorithms implemented by community health workers using malaria rapid diagnostic tests (RDTs). However, due to a changing epidemiology of fever causes in Africa, positive RDT results might not correctly reflect malaria. In this study, we modeled diagnostic predictive values for all malaria-endemic African regions as an indicator of the programmatic usefulness of RDTs in iCCM campaigns on malaria.MethodsPositive predictive values (PPVs) and negative predictive values (NPVs) of RDTs for clinical malaria were modeled. Assay-specific performance characteristics stem from the Cochrane Library and data on the proportion of malaria-attributable fevers among African febrile children aged <5 years were used as prevalence matrix.ResultsAverage country-level PPVs vary considerably. Ethiopia had the lowest PPVs (histidine-rich protein II [HRP2] assay, 17.35%; parasite lactate dehydrogenase [pLDH] assay, 39.73%), and Guinea had the highest PPVs (HRP2 assay, 95.32%; pLDH assay, 98.46%). On the contrary, NPVs were above 90% in all countries (HRP2 assay, ≥94.87%; pLDH assay, ≥93.36%).ConclusionsPPVs differed considerably within Africa when used to screen febrile children, indicating unfavorable performance of RDT-based test-and-treat algorithms in low-PPV settings. This suggests that the administration of antimalarials alone may not constitute causal treatment in the presence of a positive RDT result for a substantial proportion of patients, particularly in low-PPV settings. Therefore, current iCCM algorithms should be complemented by information on other setting-specific major causes of fever.

Diagnostic performance of HRP2-only malaria rapid diagnostic test in Ghanaian pregnant women with asymptomatic peripheral blood infection: the case of First Response® test kit

Background: The use of malaria rapid diagnostic test(RDT) enables targeted treatment that mitigates against the development of parasite drug resistance. With detection thresholds at ≥200 parasites/μL, their diagnostic performance in pregnant women may be challenging as asymptomatic infections with low parasite densities are common. Few data exist on the performance of histidine-rich protein-2 (HRP2) RDTs in Ghanaian pregnant women considering commonly occurring low parasite densities. Objective: The study sought to contribute more knowledge on test performance on First Response® test kit to guide the continuous evaluation of HRP2 RDTs in pregnancy. Methods: As part of an antimalarial drug trial in pregnancy, First Response® RDT results were compared to microscopy of peripheral blood slides in 1664 women. The diagnostic performance indicators were computed as proportions with 95% confidence intervals. The risk of having a positive RDT result was computed for age, gravidity and parasite density using binomial regression methods. Results: Parasitaemia prevalence by microscopy was 5.71%(n =95/1664) while that by RDT was 21.57%(n = 359/1664). Sensitivity was 82.11% (n=78/95), specificity was 82.09% (n=1288/1569), positive predictive value was 21.73% (n=78/359), and the likelihood ratio for a positive test was 4.58. False-negative RDT results were recorded for low parasite densities as well as densities ≥ 200/ μL while false-positive results were recorded in 281of 1664 tests. Primigravidae and younger aged women were more likely to have positive RDT results compared to multigravidae and women aged ≥ 30 yr. Conclusion: The moderate sensitivity, specificity and other diagnostic parameters reported suggest the First Response® malaria RDT is useful for detecting peripheral parasitaemia in pregnant women but the use of HRP2-only RDTs is limited by the existence of parasites with HRP2 gene deletion. The use of RDTs based on combined antigens continues to be recommended. Further research is needed on RDT performance in pregnant women with declining malaria transmission.

A same day 'test and treat' model for chronic HCV and HBV infection: Results from two community-based pilot studies in Egypt.

Prompt access to confirmatory viral load testing and staging of liver disease are key barriers in uptake of treatment for chronic hepatitis B and C infection. Our objective was to establish the feasibility of a same day 'test and treat' model in two distinct community-based settings in Egypt through use of key point-of-care(POC) portable tools for HCV and HBV viral load assessment and staging of liver disease followed by treatment initiation. Community sites were a village in northern Egypt (site 1) and a government office in Cairo (site 2). The following model was adopted: community awareness raising in the week before project initiation; site assessment to ensure optimal placement and calibration of equipment and clinical care set-up; transfer of key portable laboratory instruments to the sites (four cartridge GeneXpert, FibroScan and abdominal ultrasound); screening using rapid diagnostic tests for HCV-Ab and HBsAg, with immediate venous or finger-stick blood sampling for HCV-RNA and HBV-DNA assay, FibroScan staging of liver disease and ultrasound screening for liver cancer. At site 1, 475 individuals were screened over a single day, 125 were positive for HCV-Ab and 4 for HBsAg, 43 of 56 new HCV diagnoses were HCV RNA positive, and 3 of 4 HBsAgpositive were HBV DNA positive, 40 initiated HCV treatment, and one HBVtreatment. At site 2, 3188 individuals were screened over 3days, 157 were positive for HCV-Ab, and 27 for HBsAg; 38 of 76 new HCV diagnoses were HCV RNA positive, and 15 of 18 HBsAgpositivewere HBV-DNA positive. Across both sites, 78 patients were counselled and initiated on treatment for HCV and 12 for HBV within 3 and 4hours, respectively, of initial positive rapid diagnostic test result. We have shown the feasibility of a same day 'test and treat' model for chronic HCV and HBV infection in two community-based settings in Egypt that achieved high levels of linkage to care and initial treatment.

Incorporation of rapid diagnostic tests to improve time to antimicrobial therapy for gram-positive bacteremia and candidemia.

Even with rapid diagnostic technology to swiftly identify infectious organisms, prompt response is needed to translate results into appropriate actions. The purpose of this study was to determine if the introduction of real-time pharmacist response to positive rapid diagnostic test results would decrease time to antimicrobial therapy for gram-positive bacteremia and candidemia in a community hospital setting. A quasi-experimental study was conducted in 2 community hospitals. The study comprised 2 cohorts of adult patients who tested positive for gram-positive bacteremia involving Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, or Candida species. The preintervention cohort consisted of patients admitted from November 2017 through May 2018. The intervention cohort consisted of patients admitted from July 2018 through January 2019, after the intervention went live. The primary outcomes were time to optimal antimicrobial therapy and time to effective antimicrobial therapy. A total of 140 patients were included in the preintervention group, with 124 patients included in the intervention group. The mean (SD) time to effective therapy decreased from 13.9 (21.6) hours in the preintervention group to 8.6 (12.5) hours in the intervention group (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.89-1.48; P = 0.29). The mean (SD) time to optimal therapy significantly decreased from 53.7 (57.7) hours in the preintervention group to 38.4 (31.5) hours in the intervention group (HR, 1.73; 95% CI, 1.33-2.26; P < 0.001). The introduction of real-time pharmacist response to positive rapid diagnostic test results led to a significant decrease in time to optimal antimicrobial therapy but did not significantly affect time to effective therapy. The results showed that the allocation of limited resources of a community hospital to such a stewardship program is justifiable.

Community health workers provide integrated community case management using malaria rapid diagnostic test kits.

Throughout Nigeria malaria is an endemic disease. Efforts to treat malaria can also be combined with other illnesses including pneumonia and diarrhea, which are killing children under five years of age. The use of Rapid Diagnostic Test (RDT) aids early diagnosis of malaria and informs when other illnesses should be considered. Those with positive RDT results should be treated with Artemisinin-based Combination Therapy (ACTs), while those with negative RDTs results are further investigated for pneumonia and diarrhea. Critical health systems challenges such as human resource constraints mean that community case management (CCM) and community health workers such as volunteers called Community Directed Distributors (CDDs) can therefore play an important role in diagnosing and treating malaria. This repost described an effort to monitor and document the performance of trained CDDs in providing quality management of febrile illnesses including the use of RDTs. The program trained one hundred and fifty-two (152) CDDs on the use of RDTs to test for malaria and give ACTs for positive RDTs results, cotrimoxazole for the treatment of pneumonia and Oral rehydration solution and zinc for diarrhea They were also taught to counsel on compliance medicine, identify adverse reactions, and keep accurate records. The CDDs worked for 12 Calendar months. Their registers were retrieved and audited using a checklist to document client complaints, tests done, test results and treatment provided. No client identifying information was collected. There were 32 (21%) male CDDs and 120 (79%) females. The overall mean age of the CDDs was 36.8 (±8.7) years old. 89% of the male CDDs provided correct treatment based on RDT results compared to 97.6% of the female CDDs, a statistically significant difference. Likewise CDDs younger than 36 years of age provided 92.7% correct case management compared to those 36 years and older (98.4%). The difference between the age groups was also significant. There was a strong association between CDDs dispensing ACTs with positive RDT results. In RDT negative cases, the most common course of action was dispensing antibiotics (43.2%), followed by referring the patients (30.34%) and the providing ORS (24.1%). Volunteer CDDs who are community members can adhere to treatment protocols and guidelines and comply with performance standards. The next step is scaling this approach to a state-wide level.

Spatial heterogeneity can undermine the effectiveness of country-wide test and treat policy for malaria: a case study from Burkina Faso.

BackgroundConsiderable debate has arisen regarding the appropriateness of the test and treat malaria policy broadly recommended by the World Health Organization. While presumptive treatment has important drawbacks, the effectiveness of the test and treat policy can vary considerably across regions, depending on several factors such as baseline malaria prevalence and rapid diagnostic test (RDT) performance.MethodsTo compare presumptive treatment with test and treat, generalized linear mixed effects models were fitted to data from 6510 children under five years of age from Burkina Faso’s 2010 Demographic and Health Survey.ResultsThe statistical model results revealed substantial regional variation in baseline malaria prevalence (i.e., pre-test prevalence) and RDT performance. As a result, a child with a positive RDT result in one region can have the same malaria infection probability as a demographically similar child with a negative RDT result in another region. These findings indicate that a test and treat policy might be reasonable in some settings, but may be undermined in others due to the high proportion of false negatives.ConclusionsHigh spatial variability can substantially reduce the effectiveness of a national level test and treat malaria policy. In these cases, region-specific guidelines for malaria diagnosis and treatment may need to be formulated. Based on the statistical model results, proof-of-concept, web-based tools were created that can aid in the development of these region-specific guidelines and may improve current malaria-related policy in Burkina Faso.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1565-2) contains supplementary material, which is available to authorized users.

High-Resolution Plasmodium falciparum Malaria Risk Mapping in Mutasa District, Zimbabwe: Implications for Regaining Control.

In Zimbabwe, more than half of malaria cases are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. The objectives of this study were to develop a prediction model based on environmental risk factors and obtain seasonal malaria risk maps for Mutasa District, one of the worst affected districts in Manicaland Province. From October 2012 to September 2015, 483 households were surveyed, and 104 individuals residing within 69 households had positive rapid diagnostic test results. Logistic regression was used to model the probability of household positivity as a function of the environmental covariates extracted from high-resolution remote sensing data sources. Model predictions and prediction standard errors were generated for the rainy and dry seasons. The resulting maps predicted elevated risk during the rainy season, particularly in low-lying areas bordering Mozambique. In contrast, the risk of malaria was low across the study area during the dry season with foci of malaria risk scattered along the northern and western peripheries of the study area. These findings underscore the need for strong cross-border malaria control initiatives to complement country-specific interventions.

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses

BackgroundIn Ethiopia a tiebreaker algorithm using 3 rapid diagnostic tests (RDTs) in series is used to diagnose HIV. Discordant results between the first 2 RDTs are resolved by a third ‘tiebreaker’ RDT. Médecins Sans Frontières uses an alternate serial algorithm of 2 RDTs followed by a confirmation test for all double positive RDT results. The primary objective was to compare the performance of the tiebreaker algorithm with a serial algorithm, and to evaluate the addition of a confirmation test to both algorithms. A secondary objective looked at the positive predictive value (PPV) of weakly reactive test lines.MethodsThe study was conducted in two HIV testing sites in Ethiopia. Study participants were recruited sequentially until 200 positive samples were reached. Each sample was re-tested in the laboratory on the 3 RDTs and on a simple to use confirmation test, the Orgenics Immunocomb Combfirm® (OIC). The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing.Results2620 subjects were included with a HIV prevalence of 7.7%. Each of the 3 RDTs had an individual specificity of at least 99%. The serial algorithm with 2 RDTs had a single false positive result (1 out of 204) to give a PPV of 99.5% (95% CI 97.3%-100%). The tiebreaker algorithm resulted in 16 false positive results (PPV 92.7%, 95% CI: 88.4%-95.8%). Adding the OIC confirmation test to either algorithm eliminated the false positives. All the false positives had at least one weakly reactive test line in the algorithm. The PPV of weakly reacting RDTs was significantly lower than those with strongly positive test lines.ConclusionThe risk of false positive HIV diagnosis in a tiebreaker algorithm is significant. We recommend abandoning the tie-breaker algorithm in favour of WHO recommended serial or parallel algorithms, interpreting weakly reactive test lines as indeterminate results requiring further testing except in the setting of blood transfusion, and most importantly, adding a confirmation test to the RDT algorithm. It is now time to focus research efforts on how best to translate this knowledge into practice at the field level.Trial registrationClinical Trial registration #: NCT01716299

Malaria rapid diagnostic test in children: The Zamfara, Nigeria experience.

Background:Malaria remains a major cause of under-five morbidity and mortality in Nigeria, and prompt diagnosis occupies a strategic position in its management. Malaria rapid diagnostic test (RDT), a nontechnical, easy to perform test promises to meet this need. It is important to locally document the usefulness of the use of RDT in making prompt malaria diagnosis in children.Objective:To determine the prevalence of malaria and evaluate the diagnostic performance of malaria RDT kit in febrile under-five children presenting to a Tertiary Health Facility in Gusau, North-Western Nigeria.Materials and Methods:A cross-sectional study of children aged 6-59 months, evaluated for malaria in a tertiary health facility from August 2012 to January 2013. Information was obtained from care providers of all subjects with fever and a presumptive diagnosis of malaria. All subjects were investigated using Giemsa stain microscopy and Carestart™ malaria RDT.Results:The prevalence of malaria in 250 febrile under-five children was 54%. Three-quarter (79%) of the children received inappropriate nonrecommended antimalaria prior to their presentation, including 20% who received chloroquine. The overall sensitivity of RDT was 40.3%. The specificity, positive and negative predictive values were 89.6%, 81.8%, and 56.5%, respectively.Conclusion:Use of RDT should be encouraged for screening and diagnosis using a protocol such that febrile children with positive RDT results are confirmed as having malaria while those with negative results are further evaluated using microscopy.

Elevated dry-season malaria prevalence associated with fine-scale spatial patterns of environmental risk: a case–control study of children in rural Malawi

BackgroundUnderstanding the role of local environmental risk factors for malaria in holo-endemic, poverty-stricken settings will be critical to more effectively implement- interventions aimed at eventual elimination. Household-level environmental drivers of malaria risk during the dry season were investigated in rural southern Malawi among children < five years old in two neighbouring rural Traditional Authority (TA) regions dominated by small-scale agriculture.MethodsTen villages were randomly selected from TA Sitola (n = 6) and Nsamala (n = 4). Within each village, during June to August 2011, a census was conducted of all households with children under-five and recorded their locations with a geographic position system (GPS) device. At each participating house, a nurse administered a malaria rapid diagnostic test (RDT) to children under five years of age, and a questionnaire to parents. Environmental data were collected for each house, including land cover within 50-m radius. Variables found to be significantly associated with P. falciparum infection status in bivariate analysis were included in generalized linear models, including multivariate logistic regression (MLR) and multi-level multivariate logistic regression (MLLR). Spatial clustering of RDT status, environmental factors, and Pearson residuals from MLR and MLLR were analysed using the Getis-Ord Gi* statistic.ResultsOf 390 children enrolled from six villages in Sitola (n = 162) and four villages in Nsamala (n = 228), 45.6% tested positive (n = 178) for Plasmodium infection by RDT. The MLLR modelled the statistical relationship of Plasmodium positives and household proximity to agriculture (<25-m radius), controlling for the child sex and age (in months), bed net ownership, elevation, and random effects intercepts for village and TA-level unmeasured factors. After controlling for area affects in MLLR, proximity to active agriculture remained a significant predictor of positive RDT result (OR 2.80, 95% CI 1.41-5.55). Mapping of Pearson residuals from MLR showed significant clustering (Gi* z > 2.58, p < 0.01) predominantly within TA Sitola, while residuals from MLLR showed no such clustering.ConclusionThis study provides evidence for significant, dry-season heterogeneity of malaria prevalence strongly linked to peridomestic land use, and particularly of elevated risk associated with nearby crop production.

Strict adherence to malaria rapid test results might lead to a neglect of other dangerous diseases: a cost benefit analysis from Burkina Faso

BackgroundMalaria rapid diagnostic tests (RDTs) have generally been found reliable and cost-effective. In Burkina Faso, the adherence of prescribers to the negative test result was found to be poor. Moreover, the test accuracy for malaria-attributable fever (MAF) is not the same as for malaria infection. This paper aims at determining the costs and benefits of two competing strategies for the management of MAF: presumptive treatment for all or use of RDTs.MethodsA cost benefit analysis was carried out using a decision tree, based on data previously obtained, including a randomized controlled trial (RCT) recruiting 852 febrile patients during the dry season and 1,317 in the rainy season. Cost and benefit were calculated using both the real adherence found by the RCT and assuming an ideal adherence of 90% with the negative result. The main parameters were submitted to sensitivity analysis.Results and discussionAt real adherence, the test-based strategy was dominated. Assuming ideal adherence, at the value of 525 € for a death averted, the total cost of managing 1,000 febrile children was 1,747 vs. 1,862 € in the dry season and 1,372 vs. 2,138 in the rainy season for the presumptive vs. the test-based strategy. For adults it was 2,728 vs. 1,983 and 2,604 vs. 2,225, respectively. At the subsidized policy adopted locally, assuming ideal adherence, the RDT would be the winning strategy for adults in both seasons and for children in the dry season.At sensitivity analysis, the factors most influencing the choice of the better strategy were the value assigned to a death averted and the proportion of potentially severe NMFI treated with antibiotics in patients with false positive RDT results. The test-based strategy appears advantageous for adults if a satisfactory adherence could be achieved. For children the presumptive strategy remains the best choice for a wide range of scenarios.ConclusionsFor RDTs to be preferred, a positive result should not influence the decision to treat a potentially severe NMFI with antibiotics. In the rainy season the presumptive strategy always remains the better choice for children.

Low prevalence of Plasmodium falciparum antigenaemia among asymptomatic HAART-treated adults in an urban cohort in Uganda

BackgroundPresumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV).MethodsWithin an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect Plasmodium falciparum antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months.ResultsOf the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic P. falciparum antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months.ConclusionsIn an urban area of low to moderate stable malaria transmission, there was low HRP2 P. falciparum antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.

Improving Rational Treatment of Malaria: Perceptions and Influence of RDTs on Prescribing Behaviour of Health Workers in Southeast Nigeria

IntroductionDevelopments in rapid diagnostic tests (RDTs) have opened new possibilities for improved remote malaria diagnosis that is independent of microscopic diagnosis. Studies in some settings have tried to assess the influence of RDTs on the prescribing behaviour of health workers, but such information is generally lacking in Nigeria and many parts of sub-Saharan Africa. This study analysed health workers' perceptions of RDTs and their potential influence on their prescribing and treatment practices after their introduction.MethodsThe study was conducted in four health centers in the Enugu East local government of Enugu State, Nigeria. All 32 health workers in the health centers where RDTs were deployed were interviewed by field workers. Information was sought on their perception of symptoms-based, RDT-based, and microscopy-based malaria diagnoses. In addition, prescription analysis was carried out on 400 prescriptions before and 12 months after RDT deployment.ResultsThe majority of the health workers perceived RDTs to be more effective for malaria diagnosis than microscopy and clinical diagnosis. They also felt that the benefits of RDTs included increased use of RDTs in the facilities and the tendency to prescribe more Artemisinin-based combination therapies (ACTs) and less chloroquine and SP. Some of the health workers experienced some difficulties in the process of using RDT kits. ACTs were prescribed in 74% of RDT-negative results.Conclusions/SignificanceRDT-supported malaria diagnosis may have led to the overprescription of ACTs, with the drug being prescribed to people with RDT-negative results. However, the prescription of other antimalarial drugs that are not first-line drugs has been reduced. Efforts should be made to encourage health workers to trust RDT results and prescribe ACTs only to those with positive RDT results. In-depth studies are needed to determine why health workers continue to prescribe ACTs in RDT-negative results.