Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis (original) (raw)
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The American journal of tropical medicine and hygiene, 2008
In an area with unstable malaria transmission, detection of Plasmodium falciparum infection in 379 symptomatic individuals was assessed by microscopy and three polymerase chain reaction (PCR) methodologies. P. falciparum infection was detected in 25% of patients by microscopy, 37% by nested PCR, 41% by merozoite surface protein-2 (MSP-2) PCR, and 45% by a ligase detection reaction-fluorescent microsphere assay (LDR-FMA). Of the 64 individuals who were LDR-FMA positive, microscopy negative and did not receive treatment, 8 (12.5%) had persistent symptoms and returned for treatment. Malaria attributable fraction (MAF) in symptomatic individuals was 14.6% by microscopy (95% confidence interval [CI] = 6.6-21.8%) and 28.2% by nested PCR (95% CI = 17.9-37.2%). In this highland area, P. falciparum infection in symptomatic individuals is detected more frequently by PCR than microscopy, and most frequently by LDR-FMA. P. falciparum infection appears to resolve without treatment in most LDR-FM...
African Journal of Infectious Diseases, 2011
Detection of Plasmodium species by microscopy has been the gold standard for diagnosis of malaria for more than a century. Despite the fact that there is a significant decline in the number of positive cases reported from microscopy, antimalarial drugs prescriptions are on continuous increase as patients present with symptoms of malaria. This makes it difficult to establish accuracy, sensitivity and specificity of light microscopy in diagnosis of malaria in epidemic areas. This study was designed to compare microscopy with polymerase chain reaction as diagnostic methods for malaria in three epidemic areas in Kenya. A total of 356 patients presenting with malaria symptoms were diagnosed by microscopy and dried blood filter paper spots were collected from patient in Kisii, West Pokot and Narok districts. Plasmodium falciparum DNA was extracted from the dried blood filter samples. Primers specific for the Plasmodium Species were designed and used in a two step amplification of the Pfmdr gene. The PCR products were analyzed in ethidium bromide stained 1.5% agarose gel. It was found that 72 out of 350 specimens diagnosed as negative were positive for P. falciparum by nested PCR, while 6 which were microscopy positive were confirmed so by nested PCR. This study demonstrates that there is a high level of misdiagnosis which may either lead to denial for deserved treatment or undeserved treatment. Nested PCR detection of malaria parasites is a very useful complement to microscopy although it is expensive and takes long time. Additionally, smear negative patients suspected to have malaria should be subjected to PCR diagnosis to improve rational drug use. The economic burden of misdiagnosis and mistreatment of malaria outweighs that of PCR diagnosis, hence this diagnostic mode could be tenable in the long run even in rural areas.
Malaria Journal, 2021
Background The gold standard for diagnosing Plasmodium falciparum infection is microscopic examination of Giemsa-stained peripheral blood smears. The effectiveness of this procedure for infection surveillance and malaria control may be limited by a relatively high parasitaemia detection threshold. Persons with microscopically undetectable infections may go untreated, contributing to ongoing transmission to mosquito vectors. The purpose of this study was to determine the magnitude and determinants of undiagnosed submicroscopic P. falciparum infections in a rural area of western Kenya. Methods A health facility-based survey was conducted, and 367 patients seeking treatment for symptoms consistent with uncomplicated malaria in Homa Bay County were enrolled. The frequency of submicroscopic P. falciparum infection was measured by comparing the prevalence of infection based on light microscopic inspection of thick blood smears versus real-time polymerase chain reaction (RT-PCR) targeting ...
The American journal of tropical medicine and hygiene, 2016
Estimates of malaria transmission intensity (MTI) typically rely upon microscopy or rapid diagnostic testing (RDT). However, these methods are less sensitive than nucleic acid amplification techniques and may underestimate parasite prevalence. We compared microscopy, RDT, and polymerase chain reaction (PCR) for the diagnosis of Plasmodium falciparum parasitemia as part of an MTI study of 800 children and adults conducted in Lilongwe, Malawi. PCR detected more cases of parasitemia than microscopy or RDT. Age less than 5 years predicted parasitemia detected by PCR alone (adjusted odds ratio = 1.61, 95% confidence interval = 1.09-2.38, Wald P = 0.02). In addition, we identified one P. falciparum parasite with a false-negative RDT result due to a suspected deletion of the histidine-rich protein 2 (hrp2) gene and used a novel, ultrasensitive PCR assay to detect low-level parasitemia missed by traditional PCR. Molecular methods should be considered for use in future transmission studies a...
Journal of Biology Agriculture and Healthcare, 2013
One of the most pronounced problems in controlling the morbidity and mortality caused by malaria is limited access to effective diagnosis. Microscopy remains the gold standard for malaria diagnosis, but it is labor intensive, requires significant skills and time. Thus, this study was microscopy, when it is not available. A total of 540 patients in the three states of north prospectively enrolled to compare the performance of the Pf RDTs, and nested polymerase chain reaction (nPCR) with gold standard expert microscopy tables, using standard formulae. For RDTs was 82% and 95%, while the Sn and Sp of Pf/PAN nPCR were excellent with 98% and 100% respectively. The sensitivities of RDTs in this study were not optimal for falciparum diagnosis. Although, nPC urgency of obtaining results with suspected malaria limits its use in routine clinical practice. Thus, microscopy should remain the diagnostic test of choice for malaria in this Key word: falciparum malaria, microscopy, 1. Introduction Malaria is a severe and often rapidly fatal disease, with a high potential cost for health if diagnosis fails and an infection is missed (Bell et al. 2006) responsible for 30% childhood and 11% maternal mortality (FMOH 2005). It accounts for 300,000 deaths each year and about 60% of outpatient visits (FY 2011). for over 40% of the estimated total of malaria deaths globally (WHO 2012). Proper management of malaria cases within the first 24 hours of onset is considered to be the best way to reduce its morbidity and mortality. This would be laboratory facilities (Kamugisha et al. in time by health workers (Uzochukwu In 2010, WHO recommended a symptom-based diagnosis to parasite vigorous debate (Graz et al. 2011). This shift requires the availabilit Although, the percentage of reported suspected cases receiving a parasitological globally in 2005 to 73% in 2009 parasitological diagnosis (WHO 2011) Microscopy is considered to be the gold standard for malaria diagnosis many health facilities in sub-Saharan Africa there is a lack of properly functioning microscopes, quality systems and well-trained laboratory technicians
Acta Tropica, 2009
This paper presents estimates of P. falciparum infection prevalence in children under 5 years old in the context of a population-based household survey in Luangwa District (Lusaka Province), Zambia, an area where greater than 75% of households possess at least one insecticide-treated mosquito net (ITN). The sensitivity and specificity of an HRP-2 rapid diagnostic test (RDT) (ICT Malaria Pf ®) compared to microscopy, as well as factors associated with discordant diagnostic results are also presented. P. falciparum infection prevalence was estimated at 7.0% (95% CI 4.9-9.0%) using microscopy. Using microscopy as the gold standard, the sensitivity of the HRP-2 RDT was 100% and specificity was 91.5%; positive predictive value was estimated to be 46.7% (95% CI 36.3-57.4%). RDT discordance, or HRP-2 false positivity, was highest among older children, those in the northern part of Luangwa District, and those with a reported history of antimalarial treatment. These data suggest microscopy should remain the gold standard for estimating malaria parasite point prevalence from household surveys for monitoring and evaluation purposes.
Background: The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falci-parum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia. Methods: Two cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively. Finger prick whole blood and plasma samples were collected. The prevalence and density of P. falciparum and P. vivax parasitaemia and gametocytaemia were determined by 18S rRNA quantitative PCR (qPCR) and pfs25 and pvs25 reverse transcriptase qPCR. Antibodies against blood stage antigens apical membrane antigen-1 (AMA-1) and merozoite surface protein-1 (MSP-1 19) were measured for both species. Results: Whilst only 6 infections were detected by microscopy in 881 slides (0.7%), 107 of 845 blood samples (12.7%) were parasite positive by (DNA-based) qPCR. qPCR parasite prevalence between sites and surveys ranged from 3.8 to 19.0% for P. falciparum and 0.0 to 9.0% for P. vivax. The median density of P. falciparum infections (n = 85) was 24.4 par-asites/µL (IQR 18.0–34.0) and the median density of P. vivax infections (n = 28) was 16.4 parasites/µL (IQR 8.8–55.1). Gametocyte densities by (mRNA-based) qRT-PCR were strongly associated with total parasite densities for both P. falciparum (correlation coefficient = 0.83, p = 0.010) and P. vivax (correlation coefficient = 0.58, p = 0.010). Antibody titers against P. falciparum AMA-1 and MSP-1 19 were higher in individuals who were P. falciparum parasite positive in both surveys (p < 0.001 for both comparisons). Discussion: This study adds to the available evidence on the wide-scale presence of submicroscopic parasitaemia by quantifying submicroscopic parasite densities and concurrent gametocyte densities. There was considerable hetero-geneity in the occurrence of P. falciparum and P. vivax infections and serological markers of parasite exposure between the examined low endemic settings in Ethiopia.
Malaria Journal
Background: Zambia continues to make strides in reducing malaria burden through the use of proven malaria interventions and has recently pledged to eliminate malaria by 2021. Case management services have been scaled up at community level with rapid diagnostic tests (RDTs) providing antigen-based detection of falciparum malaria only. Key to national malaria elimination goals is the ability to identify, treat and eliminate all Plasmodium species. This study sought to determine the distribution of non-falciparum malaria and assess the performance of diagnostic tests for Plasmodium falciparum in Western and Southern Provinces of Zambia, two provinces planned for early malaria elimination. Methods: A subset of individuals' data and samples from a cross-sectional household survey, conducted during peak malaria transmission season in April and May 2017, was used. The survey collected socio-demographic information on household members and coverage of malaria interventions. Malaria testing was done on respondents of all ages using blood smears and RDTs while dried blood spots were collected on filter papers for analysis using photoinduced electron transfer polymerase chain reaction (PET-PCR). Slides were stained using Giemsa stain and examined by microscopy for malaria parasites. Results: From the 1567 individuals included, the overall prevalence of malaria was 19.4% (CI 17.5-21.4) by PCR, 19.3% (CI 17.4-21.4) by RDT and 12.9% (CI 11.3-14.7) by microscopy. Using PET-PCR as the gold standard, RDTs showed a sensitivity of 75.7% (CI 70.4-80.4) and specificity of 94.2% (CI 92.8-95.4). The positive predictive value (PPV) was 75.9% (CI 70.7-80.6) and negative predictive value (NPV) was 94.1% (CI 92.1-95.4). In contrast, microscopy for sensitivity, specificity, PPV, and NPV values were 56.9% (CI 51.1-62.5), 97.7% (CI 96.7-98.5), 85.6% (CI 80.0-90.2), 90.4% (CI 88.7-91.9), respectively. Non-falciparum infections were found only in Western Province, where 11.6% of P. falciparum infections were co-infections with Plasmodium ovale or Plasmodium malariae. Conclusion: From the subset of survey data analysed, non-falciparum species are present and occurred as mixed infections. As expected, PET-PCR was slightly more sensitive than both malaria RDTs and microscopy to detecting malaria infections.