Treatment of asymptomatic carriers with artemether-lumefantrine: an opportunity to reduce the burden of malaria?

Ogutu, Bernhards; Tiono, Alfred B.; Makanga, Michael; Premji, Zulfiqarali; Gbadoé, Adama Dodji; Ubben, David; Marrast, Anne Claire; Gaye, Oumar

doi:10.1186/1475-2875-9-30

Cited by 54 publications

(64 citation statements)

References 49 publications

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“…Lastly, there are several possible applications of our pooling strategy for malaria elimination programs. It can be applied in mass screening and treatment of asymptomatic populations, which is emerging as a potentially important strategy to facilitate malaria elimination (19). For example, mass screening and treatment are being applied as part of recent efforts to eliminate artemisinin-resistant parasites that have emerged at the ThaiCambodian border (World Health Organization, presented at the Strategy for the Containment of Artemisinin Tolerant Malaria Parasites in South-East Asia Project Meeting, Pailin, Cambodia, 2009).…”

Section: Discussionmentioning

confidence: 99%

PCR-Based Pooling of Dried Blood Spots for Detection of Malaria Parasites: Optimization and Application to a Cohort of Ugandan Children

Hsiang¹,

Lin²,

Dokomajilar

et al. 2010

J Clin Microbiol

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Sensitive, high-throughput methods to detect malaria parasites in low-transmission settings are needed. PCR-based pooling strategies may offer a solution. We first used laboratory-prepared samples to compare 2 DNA extraction and 4 PCR detection methods across a range of pool sizes and parasite densities. Pooled Chelex extraction of DNA, followed by nested PCR of cytochrome b, was the optimal strategy, allowing reliable detection of a single low-parasitemic sample (100 parasites/l) in pool sizes up to 50. This PCR-based pooling strategy was then compared with microscopy using 891 dried blood spots from a cohort of 77 Ugandan children followed for 2 years in an urban setting of low endemicity. Among 419 febrile episodes, 35 cases of malaria were detected using the PCR-based pooling strategy and 40 cases using microscopy. All five cases of malaria not detected by PCR were from samples stored for >2 years with parasitemia of <6,000/l, highlighting the issue of possible DNA degradation with long-term storage of samples. Among 472 samples collected from asymptomatic children as part of routine surveillance, 15 (3.2%) were positive by PCR-based pooling compared to 4 (0.8%) by microscopy (P ‫؍‬ 0.01). Thus, this PCR-based pooling strategy for detection of malaria parasites using dried blood spots offers a sensitive and efficient approach for malaria surveillance in low-transmission settings, enabling improved detection of asymptomatic submicroscopic infections and dramatic savings in labor and costs.Due to large-scale implementation of effective control measures, many countries where malaria is endemic are experiencing dramatic declines in disease burden. With this success has come a shift in the end goal from control to elimination (9, 10). However, when the goal is elimination, accurate detection of persons infected with malaria parasites becomes essential (11). Standard surveillance systems depend on diagnosis by microscopy, a method that is technically challenging, labor-intensive, and often inaccurate in operational settings. More recently available rapid diagnostic tests (RDTs) provide convenience and ease of use, but they have limitations in specificity, sensitivity, species identification, and cost (22).PCR-based methods for malaria parasite detection are relatively simple and provide improved sensitivity compared to microscopy and RDTs, especially in settings where infections have low parasitemia or contain mixed species (22). PCR can also be performed on dried blood spots, which are convenient for collection, storage, and transport. Nonetheless, PCR has a long turnaround time, making it an impractical tool for clinical care of individual patients. One exception would be real-time PCR, which has a short turnaround time but carries with it cost and capacity constraints that make it unavailable for rapid diagnosis in most settings. However, there is a potential role for PCR in situations where large numbers of samples are being screened: a high-throughput system could allow accurate, rapid, and cost-effective ass...

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Section: Discussionmentioning

confidence: 99%

PCR-Based Pooling of Dried Blood Spots for Detection of Malaria Parasites: Optimization and Application to a Cohort of Ugandan Children

Hsiang¹,

Lin²,

Dokomajilar

et al. 2010

J Clin Microbiol

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“…In addition, a large proportion of infected individuals in countries in which malaria is endemic are asymptomatic or subclinical. Some studies have reported microscopy-detected malaria carriage in up to 39.2% of asymptomatic individuals (4). The prevalence of asymptomatic carriers has been reported to be highest in children and adolescents due to the fact that children in regions where malaria is endemic often acquire clinical immunity to malaria from repetitive infections, resulting in the ability to tolerate malaria parasites without developing fever (4,5).…”

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confidence: 99%

“…Some studies have reported microscopy-detected malaria carriage in up to 39.2% of asymptomatic individuals (4). The prevalence of asymptomatic carriers has been reported to be highest in children and adolescents due to the fact that children in regions where malaria is endemic often acquire clinical immunity to malaria from repetitive infections, resulting in the ability to tolerate malaria parasites without developing fever (4,5). These asymptomatic carriers typically do not seek medical treatment and can serve as a reservoir of parasites not only in high-prevalence areas but also potentially in developed countries due to increased international travel (3,4).…”

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confidence: 99%

Detection of Intracellular Parasites by Use of the CellaVision DM96 Analyzer during Routine Screening of Peripheral Blood Smears

Racsa

Gander

Southern³

et al. 2015

J Clin Microbiol

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Conventional microscopy is the gold standard for malaria diagnosis. The CellaVision DM96 is a digital hematology analyzer that utilizes neural networks to locate, digitize, and preclassify leukocytes and characterize red blood cell morphology. This study compared the detection rates of Plasmodium and Babesia species on peripheral blood smears utilizing the CellaVision DM96 with the rates for a routine red blood cell morphology scan. A total of 281 slides were analyzed, consisting of 130 slides positive for Plasmodium or Babesia species and 151 negative controls. Slides were blinded, randomized, and analyzed by CellaVision and microscopy for red cell morphology scans. The technologists were blinded to prior identification results. The parasite detection rate was 73% (95/130) for CellaVision and 81% (105/130) for microscopy for positive samples. The interobserver agreement between CellaVision and microscopy was fair, as Cohen's kappa coefficient equaled 0.36. Pathologist review of CellaVision images identified an additional 15 slides with parasites, bringing the total number of detectable positive slides to 110 of 130 (85%). Plasmodium ovale had the lowest rate of detection at 56% (5 of 9); Plasmodium malariae and Babesia spp. had the highest rate of detection at 100% (3/3 and 6/6, respectively). The detection rate by CellaVision was 100% (23/23) when the parasitemia was >2.5%. The detection rate for <0.1% parasitemia was 63% (15/24). Technologists appropriately classified all negative specimens. The percentage of positive specimens detectable by CellaVision (73%) approaches results for microscopy on routine scan of peripheral blood smears for red blood cell morphology. Malaria is a global disease with an estimated 219 million cases and 660,000 deaths reported in 2010 (1). In the United States, 1,691 cases were reported in 2010, up from 767 cases in 2003, mostly from travelers to areas of endemicity (2). The recognition and diagnosis of malaria often depend on clinical signs and symptoms, including fever, headache, fatigue, myalgia, abdominal pain, nausea, vomiting, and splenomegaly. These symptoms are often nonspecific and can be easily missed by physicians unfamiliar with the presentation of malaria (3). In addition, a large proportion of infected individuals in countries in which malaria is endemic are asymptomatic or subclinical. Some studies have reported microscopy-detected malaria carriage in up to 39.2% of asymptomatic individuals (4). The prevalence of asymptomatic carriers has been reported to be highest in children and adolescents due to the fact that children in regions where malaria is endemic often acquire clinical immunity to malaria from repetitive infections, resulting in the ability to tolerate malaria parasites without developing fever (4, 5). These asymptomatic carriers typically do not seek medical treatment and can serve as a reservoir of parasites not only in high-prevalence areas but also potentially in developed countries due to increased international travel (3, 4). Effective routine scre...

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“…As programs successfully reduce malaria transmission to low levels, malaria elimination is being considered (1, 2). However, detection of infection in elimination settings will become increasingly difficult since a substantial proportion of infections will be of low parasite load or even asymptomatic (3)(4)(5)(6). To achieve elimination, malaria diagnosis needs to change from passively diagnosing ill patients in health facilities to actively detecting infections in all carriers in the community, who may or may not show clinical symptoms, as subclinically infected individuals can be significant sources of infection (7)(8)(9)(10).…”

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confidence: 99%

“…The most widely used microscopic examination is time-consuming and, being unable to detect infection of lower than 50 parasites/l (11), can miss a substantial proportion of infections in surveys of populations in areas of endemicity, especially areas with low transmission of infection (12). The antibody-based rapid diagnostic tests (RDTs), which are easy to perform, have improved sensitivities for Plasmodium falciparum infections and were proposed as a mass screening tool for malaria elimination (5). However, their sensitivities for other malaria species are often poorer than microscopy, and some cannot differentiate between active infection and past malaria experience (11).…”

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confidence: 99%

A Novel, Sensitive Assay for High-Throughput Molecular Detection of Plasmodia for Active Screening of Malaria for Elimination

et al. 2013

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bAlthough malaria remains one of the leading infectious diseases in the world, the decline in malaria transmission in some area makes it possible to consider elimination of the disease. As countries approach elimination, malaria diagnosis needs to change from diagnosing ill patients to actively detecting infections in all carriers, including asymptomatic and low-parasite-load patients. However, few of the current diagnostic methods have both the throughput and the sensitivity required. We adopted a sandwich RNA hybridization assay to detect genus Plasmodium 18S rRNA directly from whole-blood samples from Plasmodium falciparum and Plasmodium vivax patients without RNA isolation. We tested the assay with 202 febrile patients from areas where malaria is endemic, using 20 l of each blood sample in a 96-well plate format with a 2-day enzyme-linked immunosorbent assay (ELISA)-like work flow. The results were compared with diagnoses obtained using microscopy, a rapid diagnostic test (RDT), and genus-specific real-time PCR. Our assay identified all 66 positive samples diagnosed by microscopy, including 49 poorly stored samples that underwent multiple freeze-thaw cycles due to resource limitation. The assay uncovered three falsenegative samples by microscopy and four false-negative samples by RDT and agreed completely with real-time PCR diagnosis. There was no negative sample by our assay that would show a positive result when tested with other methods. The detection limit of our assay for P. falciparum was 0.04 parasite/l. The assay's simple work flow, high throughput, and sensitivity make it suitable for active malaria screening.

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Treatment of asymptomatic carriers with artemether-lumefantrine: an opportunity to reduce the burden of malaria?

Cited by 54 publications

References 49 publications

PCR-Based Pooling of Dried Blood Spots for Detection of Malaria Parasites: Optimization and Application to a Cohort of Ugandan Children

PCR-Based Pooling of Dried Blood Spots for Detection of Malaria Parasites: Optimization and Application to a Cohort of Ugandan Children

Detection of Intracellular Parasites by Use of the CellaVision DM96 Analyzer during Routine Screening of Peripheral Blood Smears

A Novel, Sensitive Assay for High-Throughput Molecular Detection of Plasmodia for Active Screening of Malaria for Elimination

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