Individual and household characteristics of persons with Plasmodium falciparum malaria in sites with varying endemicities in Kinshasa Province, Democratic Republic of the Congo

Mwandagalirwa, Melchior Kashamuka; Levitz, Lauren; Thwai, Kyaw L.; Parr, Jonathan B.; Goel, Varun; Janko, Mark; Tshefu, Antoinette; Emch, Michael; Meshnick, Steven R.; Carrel, Margaret

doi:10.1186/s12936-017-2110-7

Cited by 38 publications

(36 citation statements)

References 40 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We performed an initial assessment of enrichment by primer set using duplex, quantitative PCR (qPCR) targeting the single-copy P. falciparum lactate dehydrogenase ( pfldh ) gene and the human beta tubulin (HumTuBB) gene as previously described (Mwandagalirwa et al 2017) . We calculated enrichment by comparing Ct values of sWGA product to those of unamplified starting template.…”

Section: Initial Testing Of Candidate Swga Primer Setsmentioning

confidence: 99%

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

Morgan

Brazeau

Ngasala

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.Methods: We used whole-genome sequencing (WGS) to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. We assessed ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.Results: We identified significant decreases in the effective population sizes in both populations in the timeframe of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared large sections of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling,, we demonstrate a pair of isolates between the mainland and Zanzibar that are related at the expected level of half-siblings, consistent with recent importation.Conclusions: These findings suggest that importation plays an increasing role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.

show abstract

Section: Initial Testing Of Candidate Swga Primer Setsmentioning

confidence: 99%

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

Morgan

Brazeau

Ngasala

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Back then, an extensive mosquito bednet distribution campaign was implemented with a higher rate of implementation, especially in Kwilu. However, Mwandagalirwa et al (2017) recently reported consistent data (72% ownership vs. 45% use) in health zones of Kinshasa province, neighbouring Kwilu province (42). A low coverage during bednet distribution campaigns can explain the lower proportion of household possessing bed net.…”

Section: Discussionmentioning

confidence: 92%

“…A low coverage during bednet distribution campaigns can explain the lower proportion of household possessing bed net. Also, bednet usage is known to be higher among under-ve children and falls progressively to as low as 34% by the early twenties (42). Subsequently, the majority of participants (64%) being over ve years may account for the majority of participants not using bednets.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Plasmodium falciparum Isolates Lacking the Histidine Rich Protein 2 Gene Among Symptomatic Malaria Patients in Kwilu Province, DR. Congo.

Munyeku¹,

Musaka²,

Ernest³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundMalaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malaria-endemic countries where PfHRP2-based RDTs are widely used. However, in the last decade, the accuracy of PfHRP2-based RDTs has been challenged by the emergence of P. falciparum strains harbouring deletions of the pfhrp2 gene, resulting in false-negative results. In DR. Congo, little is known about the prevalence of the pfhrp2 gene deletion among P. falciparum isolates infecting symptomatic patients, especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread. Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malaria patients in the Kwilu province of the Democratic Republic of Congo, a low to moderate malaria transmission area.MethodsWe used secondary data from a prospective health facility-based cross-sectional study conducted on 684 individuals of all ages, seeking healthcare with symptoms suggestive of malaria from October to December 2018 in 34 randomly selected health facilities. Sociodemographic, malaria prevention and treatment practices, and clinical variables were collected using a pre-tested structured questionnaire. Patients’ medical records were used to collect additional clinical data. Blood was collected for microscopy, PfHRP2-RDT, and spotted onto Whatman filter paper for downstream genetic analysis. Genomic DNA was extracted and used to perform PCR assays for the detection and confirmation of pfhrp2 gene deletions. Data were entered and analysed using STATA15. Fischer’s exact and the Kruskal-Wallis tests were applied to look for associations between exposures and the pfhrp2 gene deletion with a level of statistical significance set at p < 0.05. ResultsThe overall prevalence of the pfhrp2 gene deletion was 9.2% (95% CI 6.7% – 12.1%). The deletion of the pfhrp2 gene was associated with health zone of origin (p=0.012) and age (p=0.019). Among false-negative PfHRP2-RDT results, only 9.9% were due to pfhrp2 gene deletion.ConclusionP. falciparum isolates with pfhrp2 gene deletions are relatively common among symptomatic patients in Kwilu province. Further investigations are needed to provide enough evidence for policy change. Meanwhile, the use of RDTs targeting PfHRP2 and pLDH antigens could limit the spread of deleted isolates.

show abstract

“…Parasite densities for all DRC and Uganda samples were determined using quantitative real-time PCR (qPCR) targeting the single-copy P. falciparum lactate dehydrogenase ( pfldh ) gene as previously described. (39, 40) P. vivax infection was diagnosed and parasite densities determined in Thailand using microscopy at the time of DBS collection and later confirmed using qualitative, species-specific 18S rRNA real-time PCR for P. vivax . (36, 38) PCR primers, probes, and reaction conditions are described in the Supplementary File .…”

Section: Methodsmentioning

confidence: 99%

A novel CRISPR-based malaria diagnostic capable of Plasmodium detection, speciation, and drug-resistance genotyping

Hennelly

et al. 2020

Preprint

View full text Add to dashboard Cite

One-sentence summary: Novel malaria SHERLOCK assays enabled robust detection, 16 speciation, and genotyping of Plasmodium spp. in diverse samples collected in Africa Abstract word count: 228 20 Manuscript word count: 5291 21 # Corresponding author information: Jonathan B. Parr, MD, MPH; 130 Mason Farm 22Rd., Chapel HillABSTRACT 24 25 CRISPR-based diagnostics are a new class of highly sensitive and specific assays with 26 multiple applications in infectious disease diagnosis. SHERLOCK, Sensitivity Enzymatic Reporter UnLOCKing, is one such CRISPR-based diagnostic that 28 combines recombinase polymerase pre-amplification, CRISPR-RNA base-pairing, and 29LwCas13a activity for nucleic acid detection. We developed SHERLOCK assays for 30 malaria capable of detecting all Plasmodium species known to cause malaria in humans 31 and species-specific detection of P. vivax and P. falciparum, the species responsible for 32 the majority of malaria cases worldwide. We validated these assays against parasite 33 genomic DNA and achieved analytical sensitivities ranging from 2.5-18.8 parasites per 34 reaction. We further tested these assays using a diverse panel of 123 clinical samples 35 from the Democratic Republic of the Congo, Uganda, and Thailand and pools of 36 Anopheles mosquitoes from Thailand. When compared to real-time PCR, the P. 37 falciparum assay achieved 94% sensitivity and 94% specificity in clinical samples. In 38 addition, we developed a SHERLOCK assay capable of detecting the dihydropteroate 39 synthetase (dhps) single nucleotide variant A581G associated with P. falciparum 40 sulfadoxine-pyrimethamine resistance. Compared to amplicon-based deep sequencing, 41 the dhps SHERLOCK assay achieved 73% sensitivity and 100% specificity when 42 applied to a panel of 43 clinical samples, with false-negative calls only at lower parasite 43 densities. These novel SHERLOCK assays have potential to spawn a new generation of 44 molecular diagnostics for malaria and demonstrate the versatility of CRISPR-based 45 diagnostic approaches. 46 47 48 Newly developed technologies that utilize Clustered, Regularly-Interspaced Palindromic 49 Repeat (CRISPR) systems have the potential to revolutionize infectious disease 50 diagnostic testing.(1) SHERLOCK, or Specific High-Sensitivity Enzymatic Reporter 51UnLOCKing, is a CRISPR-based diagnostic assay that has now been used to detect 52 dengue and Zika viruses with excellent sensitivity and specificity.(2) Its simple workflow 53 and robust performance characteristics have enabled multiplexed detection and 54 genotyping of Zika and dengue viruses, with increasingly streamlined protocols that 55 facilitate use at the point-of-care.(3, 4) SHERLOCK's potential is perhaps greatest in 56 low-resource settings where improved, reliable diagnostics are urgently needed for 57 multiple pathogens and for malaria, in particular. 58 59 Timely and accurate diagnosis is an important component of malaria control and 60 elimination efforts. The current generation of rapid diagnostic tests (RDTs) that detect 61 ...

show abstract

Individual and household characteristics of persons with Plasmodium falciparum malaria in sites with varying endemicities in Kinshasa Province, Democratic Republic of the Congo

Cited by 38 publications

References 40 publications

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

Prevalence of Plasmodium falciparum Isolates Lacking the Histidine Rich Protein 2 Gene Among Symptomatic Malaria Patients in Kwilu Province, DR. Congo.

A novel CRISPR-based malaria diagnostic capable of Plasmodium detection, speciation, and drug-resistance genotyping

Contact Info

Product

Resources

About