Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia: implication for malaria elimination

Steenkeste, Nicolas; Rogers, William O.; Okell, Lucy; Jeanne, Isabelle; Incardona, Sandra; Duval, Linda; Chy, Sophy; Hewitt, Sean; Chou, Monidarin; Socheat, Duong; Babin, François-Xavier; Ariey, Frédéric; Rogier, Christophe

doi:10.1186/1475-2875-9-108

Cited by 114 publications

(110 citation statements)

References 31 publications

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“…Yet, in malaria-endemic regions, asymptomatic malaria parasitemia, with degrees of prevalence that are geographically variable, is common. [11][12][13][14][15][16][17][18] This observation has raised two important hypotheses: 1) that asymptomatic parasitemia may contribute significantly to maintaining malaria transmission in endemic regions; and 2) different Plasmodium falciparum or P. vivax clones may differ in virulence, some more likely than others to result in symptoms. Substantial data support the former hypothesis; few data to date support the latter.…”

Section: Introductionmentioning

confidence: 99%

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

Kosek¹,

Yori²,

Gilman³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Molecular tools to distinguish strains of Plasmodium vivax are important for studying the epidemiology of malaria transmission. Two sets of markers-tandem repeat (TR) polymorphisms and MSP3α-were used to study Plasmodium vivax in patients in the Peruvian Amazon region of Iquitos. Of 110 patients, 90 distinct haplotypes were distinguished using 9 TR markers. An MSP3α polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using HhaI and AluI revealed 8 and 9 profiles, respectively, and 36 profiles when analyzed in combination. Combining TR and PCR-RFLP markers, 101 distinct molecular profiles were distinguished among these 110 patients. Nine TR markers arrayed along a 100 kB stretch of a P. vivax chromosome containing the gene for circumsporozoite protein showed non-linear linkage disequilibrium (I SA = 0.03, P = 0.001). These findings demonstrate the potential use of TR markers for molecular epidemiology studies.

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Section: Introductionmentioning

confidence: 99%

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

Kosek¹,

Yori²,

Gilman³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…At each stage, a nested PCR reaction using primers common to the cytochrome b genes of the four major human malaria species, 8 followed by an AluI restriction digest to distinguish species, was performed (cytbPCR). 9 Duplex quantitative PCR targeting the human β tubulin gene and the plasmodial methionine transfer *Address correspondence to Kimberly A. Baltzell, Departments of Family Health Care Nursing and Global Health Sciences, University of California, San Francisco, 2 Koret Way, N-431M, San Francisco, CA 94143. E-mail: kimberly.baltzell@nursing.ucsf.edu RNA (tRNA) gene (pgmet) was performed to quantify parasite density relative to human DNA, as previously described.…”

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confidence: 99%

Prevalence of PCR Detectable Malaria Infection among Febrile Patients with a Negative Plasmodium falciparum Specific Rapid Diagnostic Test in Zanzibar

Baltzell¹,

Shakely²,

Hsiang³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. We screened for malaria in 594 blood samples from febrile patients who tested negative by a Plasmodium falciparum-specific histidine-rich protein-2-based rapid diagnostic test at 12 health facilities in Zanzibar districts North A and Micheweni, from May to August 2010. Screening was with microscopy, polymerase chain reaction (PCR) targeting the cytochrome b gene (cytbPCR) of the four major human malaria species, and quantitative PCR (qPCR). The prevalence of cytbPCR-detectable malaria infection was 2% (12 of 594), including 8 P. falciparum, 3 Plasmodium malariae, and 1 Plasmodium vivax infections. Microscopy identified 4 of 8 P. falciparum infections. Parasite density as estimated by microscopy or qPCR was 4,000 parasites/μL in 5 of 8 cytbPCR-detectable P. falciparum infections. The infections that were missed by the rapid diagnostic test represent a particular challenge in malaria elimination settings and highlight the need for more sensitive point-of-care diagnostic tools to improve case detection of all human malaria species in febrile patients.Zanzibar has been the site of a substantial recent effort to reduce the overall burden of malaria. With these efforts, the prevalence of parasitologically confirmed malaria infection among febrile children presenting at primary health care facilities in Zanzibar has decreased from~25% in 2003 1 to 2% in 2010 (Shakely and others, unpublished data). Historically, Plasmodium falciparum has played a dominant role in malarial illness in Zanzibar, and elsewhere in sub-Saharan Africa, causing well over 90% of episodes of the disease 2,3 ; the remaining reported malaria infections in Zanzibar in recent years have been caused by Plasmodium malariae. 2Malaria rapid diagnostic tests (RDTs) that detect parasite antigens have improved the availability of parasite-based diagnosis for rural clinics in Africa. 4 However, the RDT currently used in most of sub-Saharan Africa and in Zanzibar at the time of this study detects histidine-rich protein-2 (HRP2), which is specific to P. falciparum, and does not detect other species of malaria parasites. 5The availability of highly sensitive molecular techniques provides an opportunity to better characterize the species of Plasmodia causing malaria in regions of sub-Saharan Africa experiencing decreasing P. falciparum transmission. The aim of this study was to assess the prevalence of polymerase chain reaction (PCR)-detectable malaria infection among febrile patients with a negative P. falciparum-specific RDT in Zanzibar.Samples for this study were from an RDT effectiveness trial (Shakely and others, unpublished data) performed in 12 Zanzibar primary health care facilities, six each in North A and Micheweni districts over a 12-week period during the high transmission season from May to August 2010. Inclusion criteria in this study were: age 2 months, a measured axillary temperature 37.5 C or history of fever in the preceding 24 hours, and absence of any danger signs of severe disease. 6After obtaining informed written consent, dried b...

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“…Such submicroscopic infections are detectable by polymerase chain reaction (PCR) and are common in areas with low and unstable malaria. [4][5][6][7] Efforts to control and eliminate malaria from Trat province on the border with Cambodia are intensifying because of the potential spread of artemisinin resistance. The detection of submicroscopic cases may facilitate containment efforts and help preserve artemisinin-based combination therapies for effective malaria treatment (Bureau of Vector-Borne Diseases, Ministry of Public Health, Thailand, unpublished data).…”

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confidence: 99%

Active Case Detection with Pooled Real-Time PCR to Eliminate Malaria in Trat Province, Thailand

Rogawski¹,

Congpuong²,

Sudathip³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. We conducted contact tracing and high-risk group screening using pooled real-time polymerase chain reaction (PCR) to support malaria elimination in Thailand. PCR detected more Plasmodium infections than the local and expert microscopists. High-throughput pooling technique reduced costs and allowed prompt reporting of results.Thailand's National Malaria Control and Elimination Strategy aims to free 80% of the country from locally acquired malaria by the year 2020 (Bureau of Vector-Borne Diseases, Ministry of Public Health, Thailand, unpublished data). However, the elimination of local transmission requires rapid detection and treatment of all infections, including those infections in asymptomatic individuals who may serve as important reservoirs.1-3 Currently, malaria case detection for surveillance depends on microscopy or rapid diagnostic tests, but both methods miss low parasite densities on the order of 10 parasites/μL. Such submicroscopic infections are detectable by polymerase chain reaction (PCR) and are common in areas with low and unstable malaria. [4][5][6][7] Efforts to control and eliminate malaria from Trat province on the border with Cambodia are intensifying because of the potential spread of artemisinin resistance. The detection of submicroscopic cases may facilitate containment efforts and help preserve artemisinin-based combination therapies for effective malaria treatment (Bureau of Vector-Borne Diseases, Ministry of Public Health, Thailand, unpublished data).Real-time PCR is a highly sensitive tool for detecting and speciating Plasmodia. Pooling samples before analysis facilitates the large-scale application of this technique for surveillance by reducing cost and analysis time. 7,8 As Thailand aims for malaria elimination, including elimination of artemisininresistant parasites, improvements in case detection are necessary. We aimed to determine if pooled real-time PCR could be integrated with the existing active case detection systems in Thailand and if so, if it would be more effective than microscopy for identifying low-density parasitemias.A single index case, with mixed P. falciparum-P. vivax infection, was identified during hospitalization for severe malaria in July of 2011 through passive case detection. This infection was likely acquired during frequent forest exposure. Two weeks after this identification, 187 residents in Bo Rai district, Trat province, Thailand (Figure 1) were contacted over 3 days according to the policies of the National Malaria Control Program of Thailand, which includes contact tracing (Case Investigation Survey) and high-risk group screening (Special Case Detection). For contact tracing, we screened neighbors within 1 km of the index case. For high-risk group screening, we screened soldiers from Khao Lan and Ban Sapanhin army camps and residents of Takang and Ban Samoh villages, which have a high proportion of Burmese Mon migrants.We administered a questionnaire to collect demographic information and risk factors for malaria, such as history of fever a...

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Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia: implication for malaria elimination

Cited by 114 publications

References 31 publications

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

Prevalence of PCR Detectable Malaria Infection among Febrile Patients with a Negative Plasmodium falciparum Specific Rapid Diagnostic Test in Zanzibar

Active Case Detection with Pooled Real-Time PCR to Eliminate Malaria in Trat Province, Thailand

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