Performance of rapid rk39 tests for the diagnosis of visceral leishmaniasis in Ethiopia: a systematic review and meta-analysis

Hagos, Dawit Gebreegziabiher; Schallig, Henk D. F. H.; Kiros, Yazezew Kebede; Abdulkadir, Mahmud; Wolday, Dawit

doi:10.1186/s12879-021-06826-w

Cited by 19 publications

(20 citation statements)

References 35 publications

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“…The rK39 RDT confirmed all microscopy and a considerable amount of the PCR positive results for suspected primary VL patients, which could indicate that its diagnostic performance might be better than previously reported in East-Africa [24,25]. However, the RDT was also positive for many unconfirmed samples.…”

Section: Plos Neglected Tropical Diseasessupporting

confidence: 67%

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PCR for detection of Leishmania donovani from microscopically negative tissue smears of suspected patients in Gondar, Ethiopia

Melkamu

Berhane²,

Jacobs³

et al. 2023

PLoS Negl Trop Dis

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Background As untreated visceral leishmaniasis (VL) is fatal, reliable diagnostics are pivotal for accurate treatment allocation. The current diagnostic algorithm for VL in Ethiopia, which is based on the rK39 rapid diagnostic test and microscopy of tissue smears, lacks sensitivity. This probably leads to missed cases and patients not receiving treatment. Methodology We conducted a retrospective study on stored microscopically negative spleen and bone marrow smears from suspected VL patients collected at the Leishmaniasis Research and Treatment Center (LRTC) in Gondar, northern Ethiopia between June 2019 and November 2020. Sociodemographic, clinical and treatment data were collected and samples were tested by real-time PCR targeting kinetoplast DNA. Principle findings Among the 191 eligible samples (135 spleen and 56 bone marrow) with a microscopically negative and valid PCR result, 119 (62.3%) were positive by PCR, although Ct values for some were high (median 33.0). Approximately three quarters of these undiagnosed primary VL (77.3%) and relapse (69.6%) patients did not receive antileishmanial treatment. Of the 56 microscopically negative bone marrow samples, 46 (82.1%) were PCR positive, which is considerably higher compared to the microscopically negative spleen samples, for which 73 out of 135 (54.1%) were PCR positive. The odds of being PCR positive were significantly higher for bone marrow aspirates and higher when white blood cell values were lower and splenomegaly (in cm) was more pronounced. Conclusions This study demonstrates that a lot of suspected VL patients remain undiagnosed and untreated. This indicates the urgent need for better diagnostics for VL in the East-African region. The outcomes of PCR positive should be closely monitored and treatment should be provided if the patient deteriorates. In resource limited settings, implementation of PCR on bone marrow aspirate smears of patients with low WBC values and splenomegaly could lead to considerable improvements in patient management.

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Section: Plos Neglected Tropical Diseasessupporting

confidence: 67%

“…However, it should be considered that the rK39 RDT positivity rate was overall very high. An important reason for this is that previous research has shown that the decision to conduct a tissue biopsy was associated with a positive rK39 RDT result, creating a bias in the sampled population [6,24].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

PCR for detection of Leishmania donovani from microscopically negative tissue smears of suspected patients in Gondar, Ethiopia

Melkamu

Berhane²,

Jacobs³

et al. 2023

PLoS Negl Trop Dis

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“…Given its complexity and infrastructural requirements, alternatives for ELISA and IFA are sought in the form of point of care (PoC) or rapid diagnostic tests (RDTs). Several RDTs have been developed for VL, mainly based on (variants of) a 39 amino acid sequence repeat of a kinesin-related protein of L. donovani, with relatively good diagnostic performance, except for East Africa [ 30 ]. In contrast, only few have been developed for CL.…”

Section: Laboratory Diagnosismentioning

confidence: 99%

Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments

2022

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This review is an update of an earlier narrative review published in 2015 on developments in the clinical management of cutaneous leishmaniasis (CL) including diagnosis, treatment, prevention and control measurements. CL is a vector-borne infection caused by the protozoan parasite Leishmania . The vector is the female sandfly. Globally, CL affects 12 million cases and annually 2 million new cases occur. CL is endemic in almost 100 countries and the total risk population is approximately 350 million people. WHO lists CL an emerging and uncontrolled disease and a neglected tropical disease. Local experience-based evidence remains the mainstay for the management of CL. Whereas intralesional therapeutic options are the first treatment option for most CL patients, those with mucocutaneous and disseminated involvement require a systemic therapeutic approach. Moreover, different Leishmania species can vary in their treatment outcomes. Therefore, species determination is critical for optimal CL clinical management. New DNA techniques allow for relatively easy Leishmania species determination, yet they are not easily implemented in resource-limited settings. There is a desperate need for novel, less toxic, and less painful treatment options, especially for children with CL. Yet, the large and well conducted studies required to provide the necessary evidence are lacking. To further control and potentially eliminate CL, we urgently need to improve vector control, and diagnostics, and we require efficient and safe vaccines. Alas, since CL primarily affects poor people, biotechnical companies dedicate little investment into the research programs that could lead to diagnostic, pharmaceutical, and vaccine innovations.

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“…It is important that any diagnostic test should be cost effective and deployable in the field within endemic regions. These requirements have favored the use of serological tests which include the DAT and detection of the rK39 antigen; however, both of these tests have limitations: the DAT requires access to a laboratory-like environment, and the rK39-based assay has varying sensitivity and specificity depending upon the endemic region ( 51 – 53 ). These limitations mean that better and more deployable diagnostics will be valuable tools for managing leishmaniasis.…”

Section: Discussionmentioning

confidence: 99%

A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection

Roberts,

Ong,

Clare

et al. 2024

mBio

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Visceral leishmaniasis is a deadly infectious disease and is one of the world’s major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans.

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Performance of rapid rk39 tests for the diagnosis of visceral leishmaniasis in Ethiopia: a systematic review and meta-analysis

Cited by 19 publications

References 35 publications

PCR for detection of Leishmania donovani from microscopically negative tissue smears of suspected patients in Gondar, Ethiopia

PCR for detection of Leishmania donovani from microscopically negative tissue smears of suspected patients in Gondar, Ethiopia

Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments

A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection

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