Rapid Diagnostic Tests Results Research Articles

Performance and utility of a rapid diagnostic test for cholera: notes from Haiti

The present study details work done at the National Public Health Laboratory in Haiti (LNSP), comparing the results of a cholera rapid diagnostic test (RDT) with culture-based methods. As of October 21, 2011, 644 specimens were tested by both RDT and culture-based method at the LNSP. The sensitivity and specificity of RDT were 95% and 80%, respectively, with a positive predictive value of 89% and negative predictive value of 91%. In resource-limited settings, the RDT has good utility and should be considered as part of the laboratory testing algorithm.

Prospective Evaluation of Three Rapid Diagnostic Tests for Diagnosis of Human Leptospirosis

BackgroundDiagnosis of leptospirosis by the microscopic agglutination test (MAT) or by culture is confined to specialized laboratories. Although ELISA techniques are more common, they still require laboratory facilities. Rapid Diagnostic Tests (RDTs) can be used for easy point-of-care diagnosis. This study aims to evaluate the diagnostic performance of the RDTs LeptoTek Dri Dot, LeptoTek Lateral Flow, and Leptocheck-WB, prospectively.MethodologyDuring 2001 to 2012, one or two of the RDTs at the same time have been applied prior to routine diagnostics (MAT, ELISA and culture) on serum specimens from participants sent in for leptospirosis diagnosis. The case definition was based on MAT, ELISA and culture results. Participants not fulfilling the case definition were considered not to have leptospirosis. The diagnostic accuracy was determined based on the 1st submitted sample and paired samples, either in an overall analysis or stratified according to days post onset of illness.ResultsThe overall sensitivity and specificity for the LeptoTek Dri Dot was 75% respectively 96%, for the LeptoTek Lateral Flow 78% respectively 95%, and for the Leptocheck-WB 78% respectively 98%. Based on the 1st submitted sample the sensitivity was low (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB), but substantially increased when the results of paired samples were combined, although accompanied by a lower specificity (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB).ConclusionsAll three tests present antibody tests contributing to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. Since the overall sensitivity of the tested RDTs did not exceed 80%, one should be cautious to rely only on an RDT result, and confirmation by reference tests is strongly recommended.

Clinical performance of an automated reader in interpreting malaria rapid diagnostic tests in Tanzania

BackgroundParasitological confirmation of malaria is now recommended in all febrile patients by the World Health Organization (WHO) to reduce inappropriate use of anti-malarial drugs. Widespread implementation of rapid diagnostic tests (RDTs) is regarded as an effective strategy to achieve this goal. However, the quality of diagnosis provided by RDTs in remote rural dispensaries and health centres is not ideal. Feasible RDT quality control programmes in these settings are challenging. Collection of information regarding diagnostic events is also very deficient in low-resource countries.MethodsA prospective cohort of consecutive patients aged more than one year from both genders, seeking routine care for febrile episodes at dispensaries located in the Bagamoyo district of Tanzania, were enrolled into the study after signing an informed consent form. Blood samples were taken for thick blood smear (TBS) microscopic examination and malaria RDT (SD Bioline Malaria Antigen Pf/Pan™ (SD RDT)). RDT results were interpreted by both visual interpretation and Deki Reader™ device. Results of visual interpretation were used for case management purposes. Microscopy was considered the “gold standard test” to assess the sensitivity and specificity of the Deki Reader interpretation and to compare it to visual interpretation.ResultsIn total, 1,346 febrile subjects were included in the final analysis. The SD RDT, when used in conjunction with the Deki Reader and upon visual interpretation, had sensitivities of 95.3% (95% CI, 90.6-97.7) and 94.7% (95% CI, 89.8–97.3) respectively, and specificities of 94.6% (95% CI, 93.5–96.1) and 95.6% (95% CI, 94.2–96.6), respectively to gold standard. There was a high percentage of overall agreement between the two methods of interpretation.ConclusionThe sensitivity and specificity of the Deki Reader in interpretation of SD RDTs were comparable to previous reports and showed high agreement to visual interpretation (>98%). The results of the study reflect the situation in real practice and show good performance characteristics of Deki Reader on interpreting malaria RDTs in the hands of local laboratory technicians. They also suggest that a system like this could provide great benefits to the health care system. Further studies to look at ease of use by community health workers, and cost benefit of the system are warranted.

Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda

BackgroundSince drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial.MethodsA survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received.ResultsAmong febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 – 40) with substantial between-cluster variation, ranging from 1% to 55%.ConclusionIn this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets.

Delayed diagnosis of Plasmodium falciparum in a soldier in Uganda: false-positive rapid diagnostic test associated with reduced repeats in pfhrp2

Rapid diagnostic tests (RDTs) are the best alternative for malaria diagnosis where a microscopic examination cannot be performed. We report here the first case of P.falciparum (false-negative) misdiagnosis in a soldier stationed in Uganda, associated with a reduced number of repeats in the P.falciparum histidine-rich protein 2 gene (pfhrp2). This gene was subsequently sequenced to determine the reason for the discordance between the RDT results and the later microscopic examination. Ten repeats of the type 2 motif AHHAHHAAD and four repeats of the type 7 motif AHHAAD were found. This isolate belongs to the group of non-sensitive parasites (<43 repeats) that are not detected by HRP2 RDTs. This inappropriate case management could have been fatal for the patient. This case confirms the problem of negative RDT results in isolated situations and of basing a therapeutic strategy on these negative results. Investigations should be conducted in Uganda and other areas of Africa to determine the presence and the geographical spread of parasites with pfhrp2 gene deletion to ensure the best performance of RDTs.

Cost-Utility of Rapid Polymerase Chain Reaction-Based Influenza Testing for High-Risk Emergency Department Patients

We evaluate the cost-effectiveness of polymerase chain reaction (PCR)-based rapid influenza testing and treatment for influenza in adult emergency department (ED) patients who are at high risk for or have evidence of influenza-related complications. We developed a cost-utility decision analysis model that assessed adult patients presenting to the ED with symptoms of an acute respiratory infection, who met the Centers for Disease Control and Prevention criteria for recommended antiviral treatment. Analysis was performed from the societal perspective, with incremental comparisons of 4 influenza testing and treatment strategies: treat none, treat according to provider judgment, treat according to results of a PCR-based rapid diagnostic test, and treat all. Treating no patients with antivirals was dominated by all other strategies that increased in both cost and benefit in the following order: treat according to provider judgment, treat according to results of a PCR-based rapid diagnostic test, and treat all. As influenza prevalence increases, treating all patients eventually dominated all other options. The economic benefit of incorporating use of rapid PCR-based influenza testing for ED patients at risk of developing influenza-related complications depends on influenza prevalence; treatment guided by physician diagnosis or rapid testing, and treatment of all patients is more effective and less costly than no treatment.

Low sensitivity of malaria rapid diagnostic tests stored at room temperature in the Brazilian Amazon Region

In remote areas of the Amazon Region, diagnosis of malaria by microscopy is practically impossible. This study aimed to evaluate the performance of two rapid diagnostic tests (RDTs) targeting different malaria antigens stored at room temperature in the Brazilian Amazon Region. Performance of the OptiMal Pf/Pan test and ICT-Now Pf/Pan test was analyzed retrospectively in 1,627 and 1,602 blood samples, respectively. Tests were performed over a 15-month period. Kits were stored at room temperature in five community health centres located in the Brazilian Amazon Region. RDT results were compared with thick blood smear (TBS) results to determine sensitivity, specificity, and accuracy of the RDT. The sensitivities of the OptiMal Pf/Pan test were 79.7% for Plasmodium falciparum malaria diagnosis and 85.7% for non-P. falciparum infections. The results showed a crude agreement of 88.5% for P. falciparum, and 88.3% for non-P. falciparum infections (Kappa index = 0.74 and 0.75, respectively). For the ICT-Now Pf/Pan test (CI 95%), the sensitivities were 87.9% for P. falciparum malaria diagnosis and 72.5% for non-P. falciparum infection. Crude agreement between the ICT-Now Pf/Pan test and TBS was 91.4% for P. falciparum and 79.7% for non-P. falciparum infection. The Kappa index was 0.81 and 0.59 for the final diagnosis of P. falciparum and non-P. falciparum, respectively. Higher levels of parasitaemia were associated with higher crude agreement between RDT and TBS. The sensitivities of RDTs stored at room temperature over a 15-month period and performed in field conditions were lower than those previously reported.

Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers’ practices in Zanzibar

BackgroundIn Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers’ practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients.MethodsSemi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children.ResultsThe following themes were identified: 1) health workers use caregivers’ history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers’ resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making.ConclusionsThis pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria.

Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration.

Background. In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of severe febrile illness, using the distributions of plasma P. falciparum HRP2 (PfHRP2) concentrations from parasitemic children with different clinical presentations.Methods. Plasma samples were collected from and peripheral blood slides prepared for 1435 children aged 6−60 months in communities and a nearby hospital in northeastern Tanzania. The study population included children with severe or uncomplicated malaria, asymptomatic carriers, and healthy control subjects who had negative results of rapid diagnostic tests. The distributions of plasma PfHRP2 concentrations among the different groups were used to model severe malaria-attributable disease.Results. The plasma PfHRP2 concentration showed a close correlation with the severity of infection. PfHRP2 concentrations of >1000 ng/mL denoted a malaria-attributable fraction of severe disease of 99% (95% credible interval [CI], 96%–100%), with a sensitivity of 74% (95% CI, 72%–77%), whereas a concentration of <200 ng/mL denoted severe febrile illness of an alternative diagnosis in >10% (95% CI, 3%–27%) of patients. Bacteremia was more common among patients in the lowest and highest PfHRP2 concentration quintiles.Conclusions. The plasma PfHRP2 concentration defines malaria-attributable disease and distinguishes severe malaria from coincidental parasitemia in African children in a moderate-to-high transmission setting.

Use of Rapid Diagnostic Tests in Malaria School Surveys in Kenya: Does their Under-performance Matter for Planning Malaria Control?

Malaria rapid diagnostic tests (RDTs) are known to yield false-positive results, and their use in epidemiologic surveys will overestimate infection prevalence and potentially hinder efficient targeting of interventions. To examine the consequences of using RDTs in school surveys, we compared three RDT brands used during a nationwide school survey in Kenya with expert microscopy and investigated the cost implications of using alternative diagnostic approaches in identifying localities with differing levels of infection. Overall, RDT sensitivity was 96.1% and specificity was 70.8%. In terms of classifying districts and schools according to prevalence categories, RDTs were most reliable for the < 1% and > 40% categories and least reliable in the 1–4.9% category. In low-prevalence settings, microscopy was the most expensive approach, and RDT results corrected by either microscopy or polymerase chain reaction were the cheapest. Use of polymerase chain reaction–corrected RDT results is recommended in school malaria surveys, especially in settings with low-to-moderate malaria transmission.

Genetic deletion of HRP2 and HRP3 in Indian Plasmodium falciparum population and false negative malaria rapid diagnostic test

Genetic polymorphisms in diagnostic antigens are important factors responsible for variable performance of rapid diagnostic tests. Additionally, the failure of antigen expression due to gene deletion may also contribute to variable performance. We report Indian Plasmodium falciparum field isolates lacking both Pfhrp2 and Pfhrp3 genes leading to false negative results of rapid diagnostic tests. The study highlights need to determine the prevalence of P. falciparum isolates lacking these genes in larger field populations in India.

SMS based external quality assessment of reading and interpretation of malaria rapid diagnostic tests: Preliminary results among more than 2000 end-users in the Democratic Republic of the Congo

Background Rapid diagnostic tests (RDT) are increasingly replacing microscopy for diagnosis of malaria in endemic settings. Although RDTs are simple and robust, errors in the post analytical phase i.e. in reading and interpretation of the RDT result, are not uncommon. In the Democratic Republic of the Congo (DRC) malaria is endemic, and malaria RDTs have been introduced since 2010. In JuneJuly 2012, an external quality assessment (EQA) addressing correct reading and interpretation of the three band malaria RDT recommended by the National Malaria Control Programme was organized among end-users in DRC.

Acceptability of Rapid Diagnostic Test-Based Management of Malaria among Caregivers of Under-Five Children in Rural Ghana

IntroductionWHO now recommends test-based management of malaria (TBMM) across all age-groups. This implies artemisinin-based combination treatment (ACT) should be restricted to rapid diagnostic test (RDT)-positive cases. This is a departure from what caregivers in rural communities have been used to for many years.MethodsWe conducted a survey among caregivers living close to 32 health centres in six districts in rural Ghana and used logistic regression to explore factors likely to influence caregiver acceptability of RDT based case management and concern about the denial of ACT on account of negative RDT results. Focus group discussions were conducted to explain the quantitative findings and to elicit further factors.ResultsA total of 3047 caregivers were interviewed. Nearly all (98%) reported a preference for TBMM over presumptive treatment. Caregivers who preferred TBMM were less likely to be concerned about the denial of ACT to their test-negative children (O.R. 0.57, 95%C.I. 0.33–0.98). Compared with caregivers who had never secured national health insurance cover, caregivers who had valid (adjusted O.R. 1.30, 95% CI 1.07–1.61) or expired (adjusted O.R. 1.38, 95% CI 1.12–1.73) insurance cover were more likely to be concerned about the denial of ACT to their RDT-negative children. Major factors that promote TBMM acceptability include the perception that a blood test at health centre level represents improvement in the quality of care, leads to improvement in treatment outcomes, and offers opportunity for better communication between health workers and caregivers. Acceptability is also enhanced by engaging caregivers in the procedures of the test. Apprehensions about negative health worker attitude could however undermine acceptance.ConclusionTest (RDT)-based management of malaria in under-five children is likely to be acceptable to caregivers in rural Ghana. The quality of caregiver-health worker interaction needs to be improved if acceptability is to be sustained.

Placental Malaria is Associated With Increased Risk of Nonmalaria Infection During the First 18 Months of Life in a Beninese Population

Several studies have shown that the risk of malaria infection increases for children born to a mother with placental malaria infection. An immune tolerance phenomenon has been hypothesized. We addressed whether Plasmodium falciparum placental infection could additionally be associated with the risk of nonmalaria fevers in infants. From 2007 to 2009, 553 infants were followed up from birth to 18 months in Benin. The occurrence of fever was actively screened by trained community workers. Malaria fevers (temperature >37.5°C with positive results of rapid diagnostic test or thick blood smear) were excluded from analysis. The association between placental malaria infection and the number of total, gastrointestinal, and respiratory febrile episodes was explored using binomial negative regression, with adjustment for maternal age, parity, parents' schooling, socioeconomic level, sex, village of birth, season of birth, prematurity, Apgar score and nutritional status. The prevalence of placental malaria infection was 11.2%. During a median follow-up of 17.8 months, 624 nonmalaria fevers were registered. Placental malaria infection was associated with a higher risk of nonmalaria fever episodes (adjusted incidence rate ratio, 1.4; 95% confidence interval, 1.1-1.8) as well as gastrointestinal (1.6; 1.1-2.5) and respiratory (1.5; 1.1-2.1) febrile syndromes. The same pattern was obtained when considering consultations after the age of 6 months. These results suggest an association between placental malaria infection and nonmalaria infections in the first 18 months of life. Immune tolerance could lead to impaired immune development not specific to malaria infections in infants born to mothers with placental malaria infection, but further studies are needed.

Using community-owned resource persons to provide early diagnosis and treatment and estimate malaria burden at community level in north-eastern Tanzania

BackgroundAlthough early diagnosis and prompt treatment is an important strategy for control of malaria, using fever to initiate presumptive treatment with expensive artemisinin combination therapy is a major challenge; particularly in areas with declining burden of malaria. This study was conducted using community-owned resource persons (CORPs) to provide early diagnosis and treatment of malaria, and collect data for estimation of malaria burden in four villages of Korogwe district, north-eastern Tanzania.MethodsIn 2006, individuals with history of fever within 24 hours or fever (axillary temperature ≥37.5°C) at presentation were presumptively treated using sulphadoxine/pyrimethamine. Between 2007 and 2010, individuals aged five years and above, with positive rapid diagnostic tests (RDTs) were treated with artemether/lumefantrine (AL) while under-fives were treated irrespective of RDT results. Reduction in anti-malarial consumption was determined by comparing the number of cases that would have been presumptively treated and those that were actually treated based on RDTs results. Trends of malaria incidence and slide positivity rates were compared between lowlands and highlands.ResultsOf 15,729 cases attended, slide positivity rate was 20.4% and declined by >72.0% from 2008, reaching <10.0% from 2009 onwards; and the slide positivity rates were similar in lowlands and highlands from 2009 onwards. Cases with fever at presentation declined slightly, but remained at >40.0% in under-fives and >20.0% among individuals aged five years and above. With use of RDTs, cases treated with AL decreased from <58.0% in 2007 to <11.0% in 2010 and the numbers of adult courses saved were 3,284 and 1,591 in lowlands and highlands respectively. Malaria incidence declined consistently from 2008 onwards; and the highest incidence of malaria shifted from children aged <10 years to individuals aged 10–19 years from 2009.ConclusionsWith basic training, supervision and RDTs, CORPs successfully provided early diagnosis and treatment and reduced consumption of anti-malarials. Progressively declining malaria incidence and slide positivity rates suggest that all fever cases should be tested with RDTs before treatment. Data collected by CORPs was used to plan phase 1b MSP3 malaria vaccine trial and will be used for monitoring and evaluation of different health interventions. The current situation indicates that there is a remarkable changing pattern of malaria and these areas might be moving from control to pre-elimination levels.

Accuracy of rapid tests for malaria and treatment outcomes for malaria and non-malaria cases among under-five children in rural Ghana.

BackgroundWHO now recommends test-based management of malaria across all transmission settings. The accuracy of rapid diagnostic test (RDT) and the outcome of treatment based on the result of tests will influence acceptability of and adherence to the new guidelines.MethodWe conducted a study at the Kintampo hospital in rural Ghana to evaluate the performance of CareStart, a HRP-2 based RDT, using microscopy as reference. We applied IMCI treatment guidelines, restricted ACT to RDT-positive children and followed-up both RDT-positive (malaria) and RDT-negative (non-malaria) cases over 28 days.Results436 children were enrolled in the RDT evaluation and 391 (children with haemoglobin >8.0 gm/dl) were followed-up to assess treatment outcomes. Mean age was 25.4 months (s.d. 14.6). Sensitivity and specificity of the RDT were 100.0% and 73.0% respectively. Over the follow-up period, 32 (18.5%) RDT-negative children converted to positive, with 7 (4.0%) of them presenting with fever. More children in the non-malaria group made unscheduled visits than children in the malaria group (13.3% versus 7.7%) On all scheduled follow-up visits, proportion of children having a temperature higher than that recorded on day 0 was higher in the non-malaria group compared to the malaria group. Reports of unfavourable treatment outcomes by caregivers were higher among the non-malaria group than the malaria group.ConclusionsThe RDT had good sensitivity and specificity. However a minority of children who will not receive ACT based on RDT results may develop clinical malaria within a short period in high transmission settings. This could undermine caregivers' and health workers' confidence in the new guidelines. Improving the quality of management of non-malarial febrile illnesses should be a priority in the era of test-based management of malaria.Trial RegistrationClinicalTrials.gov NCT00832754

A comparative laboratory diagnosis of malaria: microscopy versus rapid diagnostic test kits

ObjectiveTo compare the two methods of rapid diagnostic tests (RDTs) and microscopy in the diagnosis of malaria. MethodsRDTs and microscopy were carried out to diagnose malaria. Percentage malaria parasitaemia was calculated on thin films and all non-acute cases of plasmodiasis with less than 0.001% malaria parasitaemia were regarded as negative. Results were simply presented as percentage positive of the total number of patients under study. The results of RDTs were compared to those of microscopy while those of RDTs based on antigen were compared to those of RDTs based on antibody. Patients' follow-up was made for all cases. ResultsAll the 200 patients under present study tested positive to RDTs based on malaria antibodies (serum) method (100%). 128 out of 200 tested positive to RDTs based on malaria antigen (whole blood) method (64%), while 118 out of 200 patients under present study tested positive to visual microscopy of Lieshman and diluted Giemsa (59%). All patients that tested positive to microscopy also tested positive to RDTs based on antigen. All patients on the second day of follow-up were non-febrile and had antimalaria drugs. ConclusionsWe conclude based on the present study that the RDTs based on malaria antigen (whole blood) method is as specific as the traditional microscopy and even appears more sensitive than microscopy. The RDTs based on antibody (serum) method is unspecific thus it should not be encouraged. It is most likely that Africa being an endemic region, formation of certain levels of malaria antibody may not be uncommon. The present study also supports the opinion that a good number of febrile cases is not due to malaria. We support WHO's report on cost effectiveness of RDTs but, recommend that only the antigen based method should possibly, be adopted in Africa and other malaria endemic regions of the world.

Integrated rapid-diagnostic-test reader platform on a cellphone.

We demonstrate a cellphone-based rapid-diagnostic-test (RDT) reader platform that can work with various lateral flow immuno-chromatographic assays and similar tests to sense the presence of a target analyte in a sample. This compact and cost-effective digital RDT reader, weighing only ~65 g, mechanically attaches to the existing camera unit of a cellphone, where various types of RDTs can be inserted to be imaged in reflection or transmission modes under light-emitting diode (LED)-based illumination. Captured raw images of these tests are then digitally processed (within less than 0.2 s per image) through a smart application running on the cellphone for validation of the RDT, as well as for automated reading of its diagnostic result. The same smart application then transmits the resulting data, together with the RDT images and other related information (e.g., demographic data), to a central server, which presents the diagnostic results on a world map through geo-tagging. This dynamic spatio-temporal map of various RDT results can then be viewed and shared using internet browsers or through the same cellphone application. We tested this platform using malaria, tuberculosis (TB) and HIV RDTs by installing it on both Android-based smartphones and an iPhone. Providing real-time spatio-temporal statistics for the prevalence of various infectious diseases, this smart RDT reader platform running on cellphones might assist healthcare professionals and policymakers to track emerging epidemics worldwide and help epidemic preparedness.

Evaluation of a rapid immunochromatographic diagnostic test for the detection of rabies from brain material of European mammals

The surveillance of rabies relies on investigations conducted on dead suspected animals or animals showing clinical signs suggestive of rabies. An immunochromatographic method based on lateral flow principle has been evaluated against a collection of brain samples mainly of European mammals including bats. The performance of this new test has been compared to the conventional gold standard methods: the fluorescent Antibody Test (FAT) and the Rapid Tissue Culture Infection Test (RTCIT). This test enabled the detection of various rabies strains belonging to rabies species 1, 5, 6 and 7 and demonstrated an overall specificity of 100% and a sensitivity of more than 88% when compared to FAT and RTCIT. A total agreement between the Rapid Immunochromatographic Diagnostic Test and conventional technique results have been obtained for European bat samples.

Rapid Diagnostic Test–Based Management of Malaria: An Effectiveness Study in Papua New Guinean Infants With Plasmodium falciparum and Plasmodium vivax Malaria

In malaria-endemic areas it is recommended that febrile children be tested for malaria by rapid diagnostic test (RDT) or blood slide (BS) and receive effective malaria treatment only if results are positive. However, RDTs are known to perform less well for Plasmodium vivax. We evaluated the safety of withholding antimalarial drugs from young Papua New Guinean children with negative RDT results in areas with high levels of both Plasmodium falciparum and P. vivax infections. Longitudinal prospective study of children aged 3-27 months visiting outpatient clinics for fever. RDT was administered at first visit. RDT and microscopy were performed if children returned because of persistent symptoms. Outcomes were rates of reattendance and occurrence of severe illnesses. Of 5670 febrile episodes, 3942 (70%) involved a negative RDT result. In 133 cases (3.4%), the children reattended the clinic within 7 days for fever, of whom 29 (0.7%) were parasitemic by RDT or microscopy. Of children who reattended, 24 (0.7%) presented with a severe illness: 2 had lower respiratory tract infections (LRTIs) with low-density P. vivax on BS; 2 received a diagnosis of P. vivax malaria on the basis of RDT but BSs were negative; 16 had LRTIs; 3 had alternative diagnoses. Of these 24, 22 were cured at day 28. Two children died of illnesses other than malaria and were RDT and BS negative at the initial and subsequent visits. Treatment for malaria based on RDT results is safe and feasible even in infants living in areas with moderate to high endemicity for both P. falciparum and P. vivax infections.