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Journal of Clinical Microbiology Mar 2021The emergence of multidrug-resistant malaria in Southeast Asia (SEA) has accelerated regional malaria elimination efforts. Most malaria in this and other... (Review)
Review
The emergence of multidrug-resistant malaria in Southeast Asia (SEA) has accelerated regional malaria elimination efforts. Most malaria in this and other low-transmission settings exists in asymptomatic individuals, which conventional diagnostic tests lack the sensitivity to detect. This has led to the development of new ultrasensitive diagnostics that are capable of detecting these low-parasitemia infections. This review summarizes the current status of ultrasensitive technologies, including PCR and loop-mediated isothermal amplification (LAMP)-based methods, as well as a newly developed ultrasensitive rapid diagnostic test (uRDT). The sensitivity, specificity, and field performance of these platforms will be examined, as well as their suitability for use in resource-limited settings to aid in malaria elimination efforts. uRDTs, with their improved sensitivity, are now able to detect approximately half of asymptomatic infections, providing a useful point-of-contact tool for malaria surveillance. The increased sensitivity and high-throughput nature of PCR-based tests make them ideal for screening large populations in places where laboratory capacity exists, and the recent commercialization of malaria LAMP kits should facilitate their adoption as a public health tool in places where such infrastructure is lacking. Finally, recent advances with dried blood spots may enable utilization of the extensive laboratory infrastructure of higher-income countries to assist with molecular surveillance in support of malaria elimination. If malaria is to be eliminated in SEA and other low-endemicity regions, then ultrasensitive diagnostics will likely play a key role in identifying and clearing the vast asymptomatic pool of infections that are common to these regions.
Topics: Asymptomatic Infections; Humans; Malaria, Falciparum; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Plasmodium falciparum; Sensitivity and Specificity
PubMed: 33148707
DOI: 10.1128/JCM.01508-20 -
Malaria Journal Jun 2019Malaria eradication globally is yet to be achieved and transmission is sustained in many endemic countries. Plasmodium falciparum continues to develop resistance to...
BACKGROUND
Malaria eradication globally is yet to be achieved and transmission is sustained in many endemic countries. Plasmodium falciparum continues to develop resistance to currently available anti-malarial drugs, posing great problems for malaria elimination. This study evaluates the frequencies of asymptomatic infection and multidrug resistance-1 (mdr-1) gene mutations in parasite isolates, which form the basis for understanding persistently high incidence in South West, Nigeria.
METHODS
A total of 535 individuals aged from 6 months were screened during the epidemiological survey evaluating asymptomatic transmission. Parasite prevalence was determined by histidine-rich protein II rapid detection kit (RDT) in healthy individuals. Plasmodium falciparum mdr-1 gene mutations were detected by polymerase chain reaction (PCR) followed by restriction enzyme digest and electrophoresis to determine polymorphism in parasite isolates. Sequencing was done to confirm polymorphism. Proportions were compared using Chi-square test at p value < 0.05.
RESULTS
Malaria parasites were detected by RDT in 204 (38.1%) individuals. Asymptomatic infection was detected in 117 (57.3%) and symptomatic malaria confirmed in 87 individuals (42.6%). Overall, individuals with detectable malaria by RDT was significantly higher in individuals with symptoms, 87 of 197 (44.2%), than asymptomatic persons; 117 of 338 (34.6%), p = 0.02. In a sub-set of 75 isolates, 18(24%) and 14 (18.6%) individuals had Pfmdr1 86Y and 1246Y mutations.
CONCLUSIONS
There is still high malaria transmission rate in Nigeria with higher incidence of asymptomatic infections. These parasites harbour mutations on Pfmdr1 which contribute to artemisinin partner drug resistance; surveillance strategies to reduce the spread of drug resistance in endemic areas are needed to eliminate the reservoir of malaria parasites that can mitigate the eradication of malaria in Nigeria.
Topics: Asymptomatic Infections; Incidence; Malaria, Falciparum; Multidrug Resistance-Associated Proteins; Mutation; Nigeria; Plasmodium falciparum; Prevalence
PubMed: 31248414
DOI: 10.1186/s12936-019-2833-8 -
PLoS Medicine May 2022Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic?
METHODS AND FINDINGS
The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated.
CONCLUSIONS
Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2.
REVIEW PROTOCOL
Open Science Framework (https://osf.io/9ewys/).
Topics: Asymptomatic Infections; COVID-19; Humans; Mass Screening; Prospective Studies; SARS-CoV-2
PubMed: 35617363
DOI: 10.1371/journal.pmed.1003987 -
Malaria Journal May 2017Malaria prevalence continues to decline across sub-Saharan Africa as a result of various intervention strategies. However, the diseases still poses a public health...
BACKGROUND
Malaria prevalence continues to decline across sub-Saharan Africa as a result of various intervention strategies. However, the diseases still poses a public health concern in the region. While symptomatic malaria is recognized and treated, asymptomatic infections become increasingly important for interrupting transmission. A cross-sectional survey was conducted to assess malaria prevalence in symptomatic and asymptomatic children in Kiwangwa ward in Bagamoyo District in Tanzania.
METHODS
Four hundred school-aged children in Kiwanga ward were recruited in the study; 200 from Kiwangwa dispensary and 200 from nearby schools. Primary health parameters were examined and blood samples collected and examined for Plasmodium falciparum prevalence using rapid diagnostic test (RDT), light microscopy (LM) and reverse transcription quantitative PCR (RT-qPCR) targeting transcripts of A-type 18s rRNA of P. falciparum. Gametocytes were detected by LM and RT-qPCR targeting transcripts of gametocyte specific marker, Pfs25.
RESULTS
Overall P. falciparum prevalence was 73.3, 40.8 and 36.3% by RT-qPCR, RDT and LM in the study area, respectively (P < 0.001). As expected symptomatic children had a significantly higher prevalence of 89, 67.5 and 64.5% by qPCR, RDT and LM, compared to 57.5, 14 and 8% in the asymptomatic group, respectively. However, gametocyte prevalence in asymptomatic individuals was higher by both LM (2%) and qPCR (14%) than in symptomatic individuals LM (0.5%) and qPCR (3%).
CONCLUSIONS
A substantial difference in prevalence of symptomatic and asymptomatic infections observed in Kiwangwa ward underpins the use of molecular tools in malaria surveillance aiming at estimating prevalence and transmission. Notably, the higher gametocytaemia observed in asymptomatic children indicates the reservoir infections and points to the need for detection and treatment of both asymptomatic and symptomatic malaria.
Topics: Adolescent; Asymptomatic Infections; Child; Cross-Sectional Studies; Female; Humans; Malaria, Falciparum; Male; Plasmodium falciparum; Prevalence; Tanzania
PubMed: 28545457
DOI: 10.1186/s12936-017-1870-4 -
Antimicrobial Agents and Chemotherapy Aug 2022Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple...
Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple parasite genotypes that could affect case management and malaria epidemiology. Here, we performed AmpSeq genotyping to capture polymorphisms associated with antimalarial resistance and the genetic diversity within natural Plasmodium falciparum infections. Known genetic polymorphisms associated with altered drug susceptibility were screened for the five most common marker genes, , , , , and , and genetic diversity was established from two known AmpSeq markers, and . Relative abundance of the different genotypes within mixed infections was calculated from the number of reads per genotype. Genotyping was performed on 117 samples, 63 from asymptomatic and 54 from symptomatic individuals. We identified up to 15 genotypes within an infection, and the median multiplicity of infection was higher in asymptomatic infections (median MOI = 5 in asymptomatics versus median MOI = 2 in symptomatics, 0.001). No genetic differentiation on parasites from asymptomatic and symptomatic individuals was found. No mutation associated with ART resistance was identified. Prevalence of the P. falciparum chloroquine resistance wild-type genotype (CVMNK) reached 80%, confirming a return to chloroquine (CQ) sensitive parasites in Cameroon. In addition, the CQ-associated resistant genotype (CVIET) was present at very low density in polyclonal infections. Persistence of low-density chloroquine resistant parasites indicates competition-survival trade-offs may contribute to maintaining genetic diversity . Thus, monitoring the expansion of these low-density genotypes in different immune backgrounds will be critical to evaluate drug policy changes.
Topics: Antimalarials; Asymptomatic Infections; Chloroquine; Drug Resistance; Folic Acid Antagonists; Genotype; Humans; Malaria; Malaria, Falciparum; Mutation; Plasmodium falciparum; Protozoan Proteins
PubMed: 35862750
DOI: 10.1128/aac.00188-22 -
Frontiers in Cellular and Infection... 2022Herein, we tested the hypothesis that Asymptomatic (Pv) infected individuals (Asym) feature different epidemiological, clinical and biochemical characteristics, as well...
INTRODUCTION
Herein, we tested the hypothesis that Asymptomatic (Pv) infected individuals (Asym) feature different epidemiological, clinical and biochemical characteristics, as well as hematological parameters, potentially predictive of clinical immunity in comparison to symptomatic Pv infected individuals (Sym).
METHODOLOGY
Between 2018 - 2021, we conducted 11 population screenings (PS, Day 0 (D0)) in 13 different riverine communities around Iquitos city, in the Peruvian Amazon, to identify Pv Sym and Asym individuals. A group of these individuals agreed to participate in a nested case - control study to evaluate biochemical and hematological parameters. Pv Asym individuals did not present common malaria symptoms (fever, headache, and chills), had a positive/negative microscopy result, a positive qPCR result, reported no history of antimalarial treatment during the last month, and were followed-up weekly until Day 21 (D21). Control individuals, had a negative malaria microscopy and qPCR result, no history of antimalarial treatment or malaria infections during the last three years, and no history of comorbidities or chronic infections.
RESULTS
From the 2159 individuals screened during PS, data revealed a low but heterogeneous Pv prevalence across the communities (11.4%), where most infections were Asym (66.7%) and submicroscopic (82.9%). A total of 29 Asym, 49 Sym, and 30 control individuals participated in the nested case - control study (n=78). Ten of the individuals that were initially Asym at D0, experienced malaria symptoms during follow up and therefore, were included in the Sym group. 29 individuals remained Asym throughout all follow-ups. High levels of eosinophils were found in Asym individuals in comparison to Sym and controls.
CONCLUSION
For the first-time, key epidemiological, hematological, and biochemical features are reported from Pv Asym infections from the Peruvian Amazon. These results should be considered for the design and reshaping of malaria control measures as the country moves toward malaria elimination.
Topics: Asymptomatic Infections; Humans; Malaria; Malaria, Vivax; Peru; Prevalence
PubMed: 36118037
DOI: 10.3389/fcimb.2022.901423 -
Clinical Microbiology and Infection :... Apr 2023To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.
OBJECTIVES
To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.
METHODS
Infants (N = 444) were enrolled at 10-14 days of life and observed weekly until 2 years of age. Stool samples were collected for each acute gastroenteritis (AGE) episode, and routine stool samples were collected monthly. Stool samples were tested for sapovirus using RT-qPCR, and positive samples were genotyped.
RESULTS
A total of 348 children completed 2 years of AGE weekly surveillance; 93 (26.7%) of them experienced sapovirus AGE. Most infections occurred after 5 months of age and mainly during the second year of life (62.4%, 58/93) and early in the rainy season. Sapovirus screening in all stools from a subset of 67 children who consistently provided samples showed sapovirus infections in 91 of 330 (27.6%) AGE episodes and in 39 of 1350 (2.9%) routine stools. In this subset, the median age at the first sapovirus AGE was 11.2 months (95% CI, 9.3-15.9 months); 38 of 67 (57%) children experienced re-infections, 19 symptomatic and 19 asymptomatic. On average, sapovirus re-infections were reported 7.2 months after symptomatic and 5.3 months after asymptomatic infections. Genogroup GI (64%, 69/108) was the most common detected. Sapovirus GI.1 was more frequently detected in AGE stool samples than in routine stool samples (47.2%, 43/91 vs. 25.6%, 10/39; p 0.005), and re-infection with the same genotype was uncommon.
DISCUSSION
The first sapovirus infections occurred at approximately 11 months of age, whereas the median time to symptomatic re-infection was 7.2 months. Re-infections with the same sapovirus genotype were rare during 2 years of life suggesting genotype-specific protection after natural infection.
Topics: Infant; Child; Humans; Reinfection; Sapovirus; Birth Cohort; Asymptomatic Infections; Caliciviridae Infections; Phylogeny; Genotype; Feces
PubMed: 36423864
DOI: 10.1016/j.cmi.2022.11.013 -
International Journal of Infectious... Jan 2021The frequency of asymptomatic SARS-CoV-2 infection with viral spread is unclear. Asymptomatic SARS-CoV-2 infection development and progression was investigated in...
BACKGROUND
The frequency of asymptomatic SARS-CoV-2 infection with viral spread is unclear. Asymptomatic SARS-CoV-2 infection development and progression was investigated in subjects undergoing mandatory quarantine on airport arrival.
METHODS
2714 subjects were tested for SARS-CoV-2 and all were quarantined for 2 weeks. Viral retesting was undertaken on symptom development and routinely at 14 days if asymptomatic. Asymptomatic, positive patients underwent viral testing every 2 days to determine viral clearance.
RESULTS
188/2714 (6.9%) patients became SARS-CoV-2 positive. On arrival, 136/188 tested positive, with 44/188 (23.4%) symptomatic and 92/188 (48.9%) asymptomatic. All 92 patients remained asymptomatic and were retested every 2 days until viral clearance. 2526 quarantined subjects remained virus free at 14 days. Viral clearance did not differ between symptomatic and asymptomatic patients (12.6 ± 1.0 days and 12.1 ± 0.4 days, respectively). Of the 52/188 (27.7%) testing negative on arrival, 27/52 subsequently became positive and developed symptoms 2-13 days after arrival. 25/188 (13.3%) remained asymptomatic and tested positive at day 14, with viral testing undertaken every 2 days in these subjects; of these, 24 remained asymptomatic, with viral clearance at 9.4 ± 0.7 days - less than for those who were asymptomatic on arrival (p < 0.002).
CONCLUSION
Asymptomatic patients with COVID-19 were more prevalent than those exhibiting symptoms, and are an infection reservoir.
Topics: Adult; Aged; Aged, 80 and over; Asymptomatic Infections; Bahrain; COVID-19; COVID-19 Testing; Cohort Studies; Female; Humans; Male; Middle Aged; Prevalence; Quarantine; SARS-CoV-2
PubMed: 33157290
DOI: 10.1016/j.ijid.2020.10.091 -
Malaria Journal Jun 2022Malaria is a major cause of morbidity and mortality worldwide. According to the World Health Organization 2021 malaria report, it is considered to be endemic in 85...
BACKGROUND
Malaria is a major cause of morbidity and mortality worldwide. According to the World Health Organization 2021 malaria report, it is considered to be endemic in 85 countries and territories. Malaria elimination programmes have also faced many challenges, such as widespread asymptomatic carriers in endemic regions, and they should be considered in malaria-control programmes in endemic areas for successful transmission interruption. This study aimed to assess the prevalence of symptomatic and asymptomatic malaria infections, and associated factors in Debre Elias district communities, Northwest Ethiopia from May to Jun 2018.
METHODS
A community-based cross-sectional study was conducted among selected kebeles in Debre Elias district, Amhara region, North-western Ethiopia. Multi-stage sampling technique was carried out to select representative households. A total of 440 randomly selected households were included, of which one individual per household was sampled for laboratory examination. Malaria prevalence was determined by light microscopy of stained blood films and using CareStart™ Malaria HRP2/pLDH (Pf/Pv) Combo rapid diagnostic test (RDT). A structured questionnaire was employed to collect socio-demographic data and associated risk factors. Data entry and analysis were carried out using Epi data 3.1 and SPSS version 23 software, respectively. The association between dependent and independent variables was explored by using bivariate and multivariate logistic regression analyses. Statistically significant association was declared at P-value of < 0.05.
RESULTS
A total of 440 (333 asymptomatic and 107 symptomatic) individuals were included in this study. The overall prevalence of malaria was 5% with the majority (59.1%) of infections caused by Plasmodium falciparum. Among asymptomatic participants, 4.8% (n = 16, 95% CI = 2.6-7.3) and 4.2% (n = 14, 95% CI = 2.1-6.5) were diagnosed and confirmed by RDT and light microscopy respectively. Similarly, the prevalence of malaria among 107 symptomatic individuals was 7.5% (n = 8, 95% CI = 2.8-12.6) by either RDT or light microscopy. Utilization of insecticide-treated net (ITN), availability of ITN, house with eave, previous history of malaria infection, and family history of malaria infection were significantly associated with malaria infection (P < 0.05).
CONCLUSION
In this study, the prevalence of asymptomatic and symptomatic malaria was moderate. Screening of both symptomatic and asymptomatic malaria in the community is very important to scale up intervention programmes.
Topics: Asymptomatic Infections; Cross-Sectional Studies; Ethiopia; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Prevalence
PubMed: 35659661
DOI: 10.1186/s12936-022-04194-7 -
Malaria Journal Jun 2023Malaria is a mosquito-borne disease that is one of the most serious public health issues globally and a leading cause of mortality in many developing countries...
BACKGROUND
Malaria is a mosquito-borne disease that is one of the most serious public health issues globally and a leading cause of mortality in many developing countries worldwide. Knowing the prevalence of both symptomatic and asymptomatic malaria on a subnational scale allows for the estimation of the burden of parasitaemia present in the transmission system, enabling targeting and tailoring of resources towards greater impact and better use of available capacity. This study aimed to determine the PCR-based point prevalence of malaria infection, by parasite species, among three high-risk populations in Mondulkiri province, Cambodia: forest rangers, forest dwellers, and forest goers.
METHODS
A cross-sectional survey was performed during the transmission season in November and December 2021. Blood samples collected on filter paper from participants (n = 1301) from all target groups were screened for Plasmodium spp using PCR.
RESULTS
Malaria prevalence among all study participants was 6.7% for any Plasmodium species. Malaria prevalence in the forest ranger group was 8.1%, was 6.8% in forest goers, and 6.4% in forest dwellers; all infections were asymptomatic. Plasmodium vivax was detected in all participant groups, while the few Plasmodium falciparum infections were found in goers and dwellers. 81% of all infections were due to P. vivax, 9% were due to P. falciparum, 3% due to Plasmodium cynomolgi, and the rest (7%) remained undefined. Gender was associated with malaria infection prevalence, with male participants having higher odds of malaria infection than female participants (OR = 1.69, 95% CI 1.08-2.64). Passively collected malaria incidence data from the Cambodian government were also investigated. Health facility-reported malaria cases, based on rapid diagnostic tests, for the period Jan-Dec 2021 were 521 Plasmodium vivax (0.89% prevalence), 34 P. falciparum (0.06%) and four P. falciparum + mixed (0.01%)-a total of 559 cases (0.95%) for all of Mondulkiri.
CONCLUSION
This reservoir of asymptomatic parasitaemia may be perpetuating low levels of transmission, and thus, new strategies are required to realize the goal of eliminating malaria in Cambodia by 2025.
Topics: Animals; Humans; Male; Female; Cambodia; Plasmodium falciparum; Cross-Sectional Studies; Malaria; Malaria, Vivax; Malaria, Falciparum; Plasmodium vivax; Plasmodium; Asymptomatic Infections; Parasitemia
PubMed: 37353790
DOI: 10.1186/s12936-023-04630-2