Negative Rapid Diagnostic Test Results Research Articles

A qualitative study on determinants of the use of malaria rapid diagnostic test and anti-malarial drug prescription practices by primary healthcare workers in Ebonyi state, Nigeria

BackgroundThe increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria.MethodsBetween March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke.ResultsThe determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker’s knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients’ demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money.ConclusionsThis evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers’ use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.

Molecular investigation of malaria-infected patients in Djibouti city (2018–2021)

BackgroundThe Republic of Djibouti is a malaria endemic country that was in pre-elimination phase in 2006–2012. From 2013, however, malaria has re-emerged in the country, and its prevalence has been increasing every year. Given the co-circulation of several infectious agents in the country, the assessment of malaria infection based on microscopy or histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDT) has shown its limitations. This study, therefore, aimed to assess the prevalence of malaria among febrile patients in Djibouti city using more robust molecular tools.MethodsAll suspected malaria cases reported to be microscopy-positive were randomly sampled (n = 1113) and included in four health structures in Djibouti city over a 4-year period (2018–2021), mainly during the malaria transmission season (January–May). Socio-demographic information was collected, and RDT was performed in most of the included patients. The diagnosis was confirmed by species-specific nested polymerase chain reaction (PCR). Data were analysed using Fisher’s exact test and kappa statistics.ResultsIn total, 1113 patients with suspected malaria and available blood samples were included. PCR confirmed that 788/1113 (70.8%) were positive for malaria. Among PCR-positive samples, 656 (83.2%) were due to Plasmodium falciparum, 88 (11.2%) Plasmodium vivax, and 44 (5.6%) P. falciparum/P. vivax mixed infections. In 2020, P. falciparum infections were confirmed by PCR in 50% (144/288) of negative RDTs. After the change of RDT in 2021, this percentage decreased to 17%. False negative RDT results were found more frequently (P < 0.05) in four districts of Djibouti city (Balbala, Quartier 7, Quartier 6, and Arhiba). Malaria occurred less frequently in regular bed net users than in non-users (odds ratio [OR]: 0.62, 95% confidence interval [CI]: 0.42–0.92).ConclusionsThe present study confirmed the high prevalence of falciparum malaria and, to a lesser extent, vivax malaria. Nevertheless, 29% of suspected malaria cases were misdiagnosed by microscopy and/or RDT. There is a need to strengthen the capacity for diagnosis by microscopy and to evaluate the possible role of P. falciparum hrp2 gene deletion, which leads to false negative cases of P. falciparum.

Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania

BackgroundHistidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania.MethodsA community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes.ResultsOf all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes.ConclusionsThis study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future.

Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: A nationwide study of symptomatic malaria patients

IntroductionFalse-negative malaria rapid diagnostic test (RDT) results amongst symptomatic malaria patients are detrimental as they could lead to ineffective malaria case management. This study determined the nationwide contribution of parasites with Pfhrp2 and Pfhrp 3 gene deletions to false negative malaria RDT results in Ghana.MethodsThis was a cross sectional study where whole blood (~2 ml) was collected from patients presenting with malaria symptoms at 100 health facilities in all the regions in Ghana from May to August 2018. An aliquot of the blood was used to prepare thin and thick blood smears, filter paper blood spots (DBS) and spot a PfHRP 2 RDT kit. The remaining blood was separated into plasma and blood cells and stored at -20°C. Plasmodium parasite density and species identity was estimated from the blood smears. Plasmodium falciparum specific 18S rRNA PCR, merozoite surface protein (msp 1) and glutamate rich protein (glurp) gene PCR were used to identify P. falciparum positive samples, which were subjected to Pfhrp 2/3 exon1-2 and exon2 genotyping.ResultsOf the 2,860 microscopically P. falciparum positive patients analyzed, 134 (4.69%) had false negative P. falciparum specific RDT results. Samples for PCR analysis was available for 127 of the false negative patients, and the analysis identified 116 (91.3%) as positive for P. falciparum. Only 58.1% (79/116) of the false negative RDT samples tested positive by msp 1 and glurp PCR. Genotyping of exon 1–2 and exon 2 of the Pfhrp 2 gene identified 12.9% (10/79) and 39.5% (31/79) of samples respectively to have deletions. Genotyping exon 1–2 and exon 2 of the Pfhrp 3 gene identified 15.2% (12/79) and 40.5% (32/79) of samples respectively to have deletions. Only 5% (4/79) of the false negative samples had deletions in both exon 1–2 and exon 2 of the Pfhrp 2 gene. Out of the 49 samples that tested positive for aldolase by luminex, 32.6% (16/49) and) had deletions in Pfhrp 2 exon 2 and 2% (1/49) had deletions in both exon 2 and exon 1–2 of the Pfhrp 2 gene.ConclusionsThe low prevalence of false negative RDT test results provides assurance that PfHRP 2 based malaria RDT kits remain effective in diagnosing symptomatic malaria patients across all the Regions of Ghana. Although there was a low prevalence of parasites with deletions in exon 2 and exon 1–2 of the Pfhrp 2 gene the prevalence of parasites with deletions in Pfhrp 2 exon 2 was about a third of the false negative RDT results. The need to ensure rapid, accurate and reliable malaria diagnosis requires continuous surveillance of parasites with Pfhrp 2 gene deletions.

Management of Late-Preterm and Term Neonates at Risk for Early-Onset Sepsis.

The management of patients at risk for a low-frequency but serious illness poses many challenges for health professionals. Neonatal early-onset sepsis (EOS) in late-preterm and term neonates is a classic example of such a low-frequency serious condition. Faced with the possibility that such an infant, even if well appearing, can develop EOS, clinicians have traditionally erred on the side of treating with antibiotics until the EOS is ruled out by some combination of a continued normal clinical examination, negative blood cultures, and negative rapid diagnostic test results. A liberal antibiotic treatment strategy resulted in a large number (as high as several hundreds) of infants being needlessly treated with antibiotics for every neonate with true EOS. This strategy has been relatively easy for clinicians to follow because the burden of administering a short course of antibiotics is relatively low, and the adverse effects of antibiotics (eg, emergence of antibiotic resistance, altered microbiome) are not immediately apparent or dramatic. In contrast, most clinicians have experienced in their careers or heard about newborn infants with catastrophic consequences or even death from EOS, especially during an era when group B streptococcal infection was more common than today. Thus, there was significant overtreatment of infants as well as much interinstitutional and interclinician variation in the frequency of antibiotic use for neonates at risk for EOS. In recent years, this calculus of weighing of a possible catastrophic event that occurs at low frequency against the invisible and delayed hazards of antibiotics has changed. Nationally and internationally, alarms are being raised about the hazards of antibiotics, the widespread emergence of bacterial resistance to antibiotics, and the drying up of …

Antimalarial drug prescribing by healthcare workers when malaria testing is negative: a qualitative study in Madagascar

BackgroundDespite the World Health Organization and the National Malaria Program of Madagascar recommending that antimalarial drugs only be prescribed for patients with positive results on malaria rapid diagnostic tests, healthcare workers continue to prescribe these drugs for cases with negative test results. We explored why and how primary healthcare workers in Madagascar continue to prescribe antimalarial drugs despite this guidance.MethodsWe purposively selected 14 medical doctors and 2 nurses from 11 primary health facilities (6 public, 5 private) in Toliara, Madagascar, and interviewed them regarding their antimalarial prescribing behaviors. Semi-structured interviews were conducted, focusing on why and how antimalarials were prescribed for clients with negative rapid diagnostic test results. Interviews were audio-recorded and transcribed verbatim, and the responses were manually coded until consistent themes emerged.ResultsThe narrative of healthcare workers regarding their continued prescribing of antimalarials despite negative test results revealed the following: (1) they prescribe antimalarials without positive test results due to their faith to give top priority to clients including the ethical value of beneficence, hope to maintain clinician’s independence, and belief in drug effectiveness; (2) they use antimalarials despite negative test results due to the availability of alternative ways to procure antimalarials; and (3) they carefully select cases to prescribe and determine specific antimalarials despite negative test results by considering the client’s physical condition, preference, and economic status. Our results indicate that healthcare workers prioritized clinician autonomy to give the best care they believed for each client they received, which led to conflict with policy administrators that urged clinicians to follow the national policy and guidelines. Moreover, healthcare workers had access to multiple sources of antimalarial drugs, and there was a lack of consistency in the program provisions that allowed alternative routes for prescribing outside of official policy.ConclusionsWe have shown how a national malarial treatment policy was translated into practice in Madagascar and have highlighted the barriers that may prevent policy success. We must attend to each of these barriers if we are to promote optimal use of antimalarial drugs.

Determinants of health workers management of patients with negative malaria rapid test result, Oyo state, Nigeria, 2016

Introduction : as part of efforts to prevent resistance to the currently effective antimalarial medicines, the World Health Organization (WHO) guidelines recommends that they should be offered only to patients with positive malaria parasitological test result. Health workers however continue to prescribe antimalarial medicines to patients with negative malaria Rapid Diagnostic Test (RDT) result. The reasons why they do so is not clearly understood. This study was carried out to identify the practices of health workers in managing patients with negative RDT results and the factors associated with such practices.

Determinants of Integrated Management of Childhood Illness (IMCI) non-severe pneumonia classification and care in Malawi health facilities: Analysis of a national facility census.

BackgroundResearch shows inadequate Integrated Management of Childhood Illness (IMCI)–pneumonia care in various low–income settings but evidence is largely from small–scale studies with limited evidence of patient–, provider– and facility–levels determinants of IMCI non–severe pneumonia classification and its management.MethodsThe Malawi Service Provision Assessment 2013–2014 included 3149 outpatients aged 2–59 months with completed observations, interviews and re–examinations. Mixed–effects logistic regression models quantified the influence of patient–, provider and facility–level determinants on having IMCI non–severe pneumonia and its management in observed consultations.FindingsAmong 3149 eligible outpatients, 590 (18.7%) had IMCI non–severe pneumonia classification in re–examination. 228 (38.7%) classified cases received first–line antibiotics and 159 (26.9%) received no antibiotics. 18.6% with cough or difficult breathing had 60–second respiratory rates counted during consultations, and conducting this assessment was significantly associated with IMCI training ever received (odds ratio (OR) = 2.37, 95% confidence interval (CI): 1.29–4.31) and negative rapid diagnostic test results (OR = 3.21, 95% CI: 1.45–7.13). Older children had lower odds of assessments than infants (OR = 48–59 months: 0.35, 95% CI: 0.16–0.75). Children presenting with any of the following complaints also had reduced odds of assessment: fever, diarrhea, skin problem or any danger sign. First–line antibiotic treatment for classified cases was significantly associated with high temperatures (OR = 3.26, 95% CI: 1.24–8.55) while older children had reduced odds of first–line treatment compared to infants (OR = 48–59 months: 0.29, 95% CI: 0.10–0.83). RDT–confirmed malaria was a significant predictor of no antibiotic receipt for IMCI non–severe pneumonia (OR = 10.65, 95% CI: 2.39–47.36).ConclusionsIMCI non–severe pneumonia care was sub–optimal in Malawi health facilities in 2013–2014 with inadequate assessments and prescribing practices that must be addressed to reduce this leading cause of mortality. Child’s symptoms and age, malaria diagnosis and provider training were primary influences on assessment and treatment practices. Current evidence could be used to better target IMCI training and support to improve pneumonia care for sick children in Malawi facilities.

Precarity and Preparedness: Non-Adherence as Institutional Work in Diagnosing and Treating Malaria in Uganda

ABSTRACTAccess to anti-malarial drugs is increasingly governed by novel regulation technologies like rapid diagnostic tests (RDTs). However, high rates of non-adherence particularly to negative RDT results have been reported, threatening the cost-effectiveness of the two interrelated goals of improving diagnosis and reducing the over-prescription of expensive anti-malarial drugs. Below I set out to reconstruct prior treatment forms like presumptive treatment of malaria by paying particular attention to their institutional groundings. I show how novel regulation technologies affect existing institutions of care and argue that the institutional work of presumptive treatment goes beyond the diagnosis and treatment of a currently observed fever episode. Instead, in contexts of precarity, through what I will call “practices of preparedness,” presumptive treatment includes a variety of practices, performances, temporalities, and opportunities that allow individuals to prepare for future episodes of fever.

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm.

Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2+)/pLDH-negative (pLDH-) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2+/pLDH+ result, 94 (34.1%) with an HRP2+/pLDH- result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2+/pLDH- results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2+/pLDH- results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.

Rapid diagnostic tests failing to detect Plasmodium falciparum infections in Eritrea: an investigation of reported false negative RDT results

BackgroundRelatively large number of false-negative malaria rapid diagnostic test (RDT) results for microscopically confirmed Plasmodium falciparum cases were reported from five of the six administrative regions of Eritrea in 2015. This activated the Ministry of Health to conduct an initial exploratory investigation. The main objective of the investigation was to confirm the sensitivity of the RDTs in the field in microscopically confirmed malaria cases, identify the possible causes of the failure and recommend further actions to be taken.MethodsA team composed of the National Malaria Control Programme, National Medicines and Food Administration and Laboratory Unit of the Ministry of Health was established to confirm the sensitivity of the SD Bioline® RDTs. A ‘Malaria RDT quality monitoring form’ was prepared and distributed to 13 health facilities selected on availability of microscopy services, experienced laboratory personnel and malaria endemicity, to carry out preliminary investigation on the suspected RDT quality defect. In parallel, field visits to central and regional medical warehouses as well as selected health facilities were conducted to assess the storage conditions, handling and operator procedures. Furthermore, joint field assessment was conducted with the manufacturer, SD Bioline RDTs. During the time frame of 15 July 2015 to 19 January 2016, 65 microscopically confirmed patients were tested with Malaria RDTs SD Bioline Pf/Pv/Mixed Combo cassettes.ResultsA total of 65 blood specimens (50 P. falciparum, 13 Plasmodium vivax and 2 mixed) confirmed microscopically were tested against the available lots of malaria RDTs. Out of the 50 P. falciparum infected blood specimens, only 10 were confirmed positive with all the lots of PfHRP-2 detecting RDTs making the false negativity rate at 80% [41/51]. The false negative result for RDT targeting PfHRP2 antigen ranged from 65% [11/17] in Gash Barka region to 100% [12/12] in Northern Red Sea Region. In addition, supervisory visits undertaken by the study team have ruled out storage, handling and operator errors as causes of false negative results as the above parameter were found to be up to standards.ConclusionThe investigation confirmed high false-negativity rate in PfHRP-2 detecting RDTs and has ruled out quality of RDTs, storage, handling and operator error as causes of the reported problem. Therefore, molecular characterization of the P. falciparum is highly recommended to explore if parasite characteristics can be considered as causes of false negative results.

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.

Health Worker Compliance with a 'Test And Treat' Malaria Case Management Protocol in Papua New Guinea.

The Papua New Guinea (PNG) Department of Health introduced a ‘test and treat’ malaria case management protocol in 2011. This study assesses health worker compliance with the test and treat protocol on a wide range of measures, examines self-reported barriers to health worker compliance as well as health worker attitudes towards the test and treat protocol. Data were collected by cross-sectional survey conducted in randomly selected primary health care facilities in 2012 and repeated in 2014. The combined survey data included passive observation of current or recently febrile patients (N = 771) and interviewer administered questionnaires completed with health workers (N = 265). Across the two surveys, 77.6% of patients were tested for malaria infection by rapid diagnostic test (RDT) or microscopy, 65.6% of confirmed malaria cases were prescribed the correct antimalarials and 15.3% of febrile patients who tested negative for malaria infection were incorrectly prescribed an antimalarial. Overall compliance with a strictly defined test and treat protocol was 62.8%. A reluctance to test current/recently febrile patients for malaria infection by RDT or microscopy in the absence of acute malaria symptoms, reserving recommended antimalarials for confirmed malaria cases only and choosing to clinically diagnose a malaria infection, despite a negative RDT result were the most frequently reported barriers to protocol compliance. Attitudinal support for the test and treat protocol, as assessed by a nine-item measure, improved across time. In conclusion, health worker compliance with the full test and treat malaria protocol requires improvement in PNG and additional health worker support will likely be required to achieve this. The broader evidence base would suggest any such support should be delivered over a longer period of time, be multi-dimensional and multi-modal.

Factors associated with the failure of Intermittent Preventive Treatment for malaria among pregnant women in Yaounde

IntroductionLe traitement préventif intermittent à la sulfadoxine-pyriméthamine (TPIp-SP) est recommandé pour prévenir le paludisme pendant la grossesse. Nous avons recherché les facteurs associés à l’échec de cette stratégie.MéthodesNous avons mené une étude cas - témoins dans deux formations sanitaires de Yaoundé, du 1er Mai 2014 au 30 Avril 2015. Les femmes enceintes sous TPIp-SP hospitalisées pour paludisme ayant un Test de Diagnostic Rapide (TDR) positif (cas) étaient comparées aux femmes enceintes sous TPIp-SP ayant un TDR négatif (témoins). Les logiciels Epi info 7 et SPSS 18.0 ont été utilisés avec P < 0,05 comme seuil de significativité.RésultatsNous avons recruté 234 sujets, 109 cas (46,6%) et 125 témoins (53,4%). Les facteurs associés retrouvés étaient: la primiparité (P=0,03; OR=1,15; IC= 0,32 - 4,10), la non utilisation de la MILDA (P=0,006; OR= 2,31; IC= 1,26 - 4,25), un antécédent d'hospitalisation pour paludisme (P=0,007; OR= 2,19; IC= 1,23 - 3,89), le début de la TPIp-SP après la 28ème semaine de grossesse (P=0,001, OR= 3,55; IC= 1,7 - 7,61). Après régression logistique, la primiparité (P=0,024; OR=2,01; IC=1,1-3,7) et un antécédent d'hospitalisation pour paludisme (P=0,001; OR=2,83; IC=1,50-5,4) restaient associés à l’échec du TPIp-SP.ConclusionUn antécédent d'hospitalisation pour accès palustre et la primiparité sont des facteurs prédictifs indépendants de l’échec de la TPIp-SP.

Health workers' compliance to rapid diagnostic tests (RDTs) to guide malaria treatment: a systematic review and meta-analysis.

BackgroundThe World Health Organization recommends malaria to be confirmed by either microscopy or a rapid diagnostic test (RDT) before treatment. The correct use of RDTs in resource-limited settings facilitates basing treatment onto a confirmed diagnosis; contributes to speeding up considering a correct alternative diagnosis, and prevents overprescription of anti-malarial drugs, reduces costs and avoids unnecessary exposure to adverse drug effects. This review aims to evaluate health workers’ compliance to RDT results and factors contributing to compliance.MethodsA PROSPERO-registered systematic review was conducted to evaluate health workers’ compliance to RDTs in sub-Saharan Africa, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published up to November 2015 were searched without language restrictions in Medline/Ovid, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus. The primary outcome was health workers treating patients according to the RDT results obtained.ResultsThe literature search identified 474 reports; 14 studies were eligible and included in the quantitative analysis. From the meta-analysis, health workers’ overall compliance in terms of initiating treatment or not in accordance with the respective RDT results was 83 % (95 % CI 80–86 %). Compliance to positive and negative results was 97 % (95 % CI 94–99 %) and 78 % (95 % CI 66–89 %), respectively. Community health workers had higher compliance rates to negative test results than clinicians. Patient expectations, work experience, scepticism of results, health workers’ cadres and perceived effectiveness of the test, influenced compliance.ConclusionsWith regard to published data, compliance to RDT appears to be generally fair in sub-Saharan Africa; compliance to negative results will need to improve to prevent mismanagement of patients and overprescribing of anti-malarial drugs. Improving diagnostic capacity for other febrile illnesses and developing local evidence-based guidelines may help improve compliance and management of negative RDT results.Trial registration: CRD42015016151 (PROSPERO)Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1218-5) contains supplementary material, which is available to authorized users.

Why do health workers give anti-malarials to patients with negative rapid test results? A qualitative study at rural health facilities in western Uganda.

BackgroundThe large-scale introduction of malaria rapid diagnostic tests (RDTs) promises to improve management of fever patients and the rational use of valuable anti-malarials. However, evidence on the impact of RDT introduction on the overprescription of anti-malarials has been mixed. This study explored determinants of provider decision-making to prescribe anti-malarials following a negative RDT result.MethodsA qualitative study was conducted in a rural district in mid-western Uganda in 2011, ten months after RDT introduction. Prescriptions for all patients with negative RDT results were first audited from outpatient registers for a two month period at all facilities using RDTs (n = 30). Facilities were then ranked according to overall prescribing performance, defined as the proportion of patients with a negative RDT result prescribed any anti-malarial. Positive and negative deviant facilities were sampled for qualitative investigation; positive deviants (n = 5) were defined ex post facto as <0.75 % and negative deviants (n = 7) as >5 %. All prescribing clinicians were targeted for qualitative observation and in-depth interview; 55 fever cases were observed and 22 providers interviewed. Thematic analysis followed the ‘framework’ approach.Results8344 RDT-negative patients were recorded at the 30 facilities (prescription audit); 339 (4.06 %) were prescribed an anti-malarial. Of the 55 observed patients, 38 tested negative; one of these was prescribed an anti-malarial. Treatment decision-making was influenced by providers’ clinical beliefs, capacity constraints, and perception of patient demands. Although providers generally trusted the accuracy of RDTs, anti-malarial prescription was driven by perceptions of treatment failure or undetectable malaria in patients who had already taken artemisinin-based combination therapy prior to facility arrival. Patient assessment and other diagnostic practices were minimal and providers demonstrated limited ability to identify alternative causes of fever. Provider perceptions of patient expectations sometimes appeared to influence treatment decisions.ConclusionsThe study found high provider adherence to RDT results, but that providers believed in certain clinical exceptions and felt they lacked alternative options. Guidance on how the RDT works and testing following partial treatment, better methods for assisting providers in diagnostic decision-making, and a context-appropriate provider behaviour change intervention package are needed.

Diagnosis of malaria: A comparison between microscopy and rapid diagnostic test among under-five children at Gusau, Nigeria

Background: Malaria remains a disease of public health concern in tropical countries. Diagnosis in such countries largely depends on clinical assessment, microscopy (as the gold standard) and recently by rapid diagnostic tests (RDTs). This study was conducted to document common presenting symptoms of malaria, compare microscopy and RDT in the diagnosis of malaria in children in Gusau, Nigeria. Materials and Methods: A cross-sectional, study of children under-five years with presumptive diagnosis of malaria that was managed at the pediatric outpatient department and emergency pediatric unit of Yariman Bakura Specialist Hospital, Gusau. All consecutive children that met the inclusion criteria were recruited over a 4 weeks period. Malaria thick film microscopy and RDTs were carried out on all children. Results: Of the 118 children enrolled, 61 (51.69%) were males while 57 (48.31%) were females. Fever and vomiting were the most common presenting complaints. Microscopy was positive in 55 (46.61%) while RDT was positive in 10 (8.47%) of the children. Only 5 (4.24%) were positive for both microscopy and RDT. Fifty-eight (49.15%) children had negative microscopy and RDT results. There was no significance when positivity of both tests were compared ( χ 2 = 0.050, P = 0.822). RDT had a sensitivity of 9.09%, a specificity of 92.06%, positive predictive value of 50.00%, and a negative predictive value of 53.70%. Conclusion: Our study observed higher positivity rate for microscopy than RDT. We recommend microscopy to be carried out on all patients suspected of having malaria where possible, even in the presence of negative RDT.

Rapid diagnostic tests for malaria and health workers' adherence to test results at health facilities in Zambia.

BackgroundIn Zambia, there has been a large scaling up of interventions to control malaria in recent years including the deployment of rapid diagnostic tests (RDTs) to improve malaria surveillance data as well as guide malaria treatment in health facilities. The practical challenge is the impact of RDT results on subsequent management of patients. This study explored the role of RDTs in malaria diagnosis and the health workers’ adherence to test results.MethodsAn observational prospective study was carried out at health centres in four districts, namely Chibombo, Chingola, Chipata, and Choma. Children under the age of five years with history of fever were recruited and the clinicians’ use of RDT results was observed to establish whether prescriptions were issued prior to the availability of parasitological results or after, and whether RDT results influenced their prescriptions.ResultsOf the 2, 393 recruited children, 2, 264 had both RDT and microscopic results. Two in three (68.6%) children were treated with anti-malarials despite negative RDT results and almost half (46.2%) of these were prescribed Coartem®. Only 465 (19.4%) of the 2,393 children were prescribed drugs before receiving laboratory results. A total of 76.5% children were prescribed drugs after laboratory results. Children with RDT positive results were 2.66 (95% CI (2.00, 3.55)) times more likely to be prescribed anti-malarial drugs. Children who presented with fever at admission (although history of fever or presence of fever at admission was an entry criterion) were 42% less likely to be prescribed an anti-malarial drug compared to children who had no fever (AOR = 0.58; 95% CI (0.52, 0.65)). It was noted that proportions of children who were RDT- and microscopy-positive significantly declined over the years from 2005 to 2008.ConclusionsRDTs may contribute to treatment of febrile illness by confirming malaria cases from non-malaria cases in children under the age of five. However, the adherence of the health workers to prescribing anti-malarials to only RDT-positive cases at health facility level will still require to be explored further as their role is crucial in more precise reporting of malaria cases in this era towards malaria elimination as the target.

Malaria, a difficult diagnosis in a febrile patient with sub-microscopic parasitaemia and polyclonal lymphocyte activation outside the endemic region, in Brazil

A case of autochthonous Plasmodium vivax malaria with sub-microscopic parasitaemia and polyclonal B-cell activation (PBA) (as reflected by positive IgM and IgG serology for toxoplasmosis, cytomegalovirus, and antinuclear and rheumatoid factors) was diagnosed by polymerase chain reaction (PCR) after consecutive negative rapid diagnostic test results and blood films. The patient, a 44-year-old man from Rio de Janeiro state, Brazil, had visited the Atlantic Forest, a tourist, non-malaria-endemic area where no autochthonous cases of ’bromeliad malaria‘ has ever been described. The characteristic pattern of fever, associated with PBA, was the clue to malaria diagnosis, despite consecutive negative thick blood smears. The study highlights a need for changes in clinical and laboratory diagnostic approaches, namely the incorporation of PCR as part of the current routine malaria diagnostic methods in non-endemic areas.

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.