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Parasite Epidemiology and Control May 2023Asymptomatic Plasmodium carriers form the majority of malaria-infected individuals in most endemic areas. A proportion of these asymptomatically infected individuals...
BACKGROUND
Asymptomatic Plasmodium carriers form the majority of malaria-infected individuals in most endemic areas. A proportion of these asymptomatically infected individuals carry gametocytes, the transmissible stages of malaria parasites, that sustain human to mosquito transmission. Few studies examine gametocytaemia in asymptomatic school children who may form an important reservoir for transmission. We assessed the prevalence of gametocytaemia before antimalarial treatment and monitored clearance of gametocytes after treatment in asymptomatic malaria children.
METHODS
A total of 274 primary school children were screened for parasitaemia by microscopy. One hundred and fifty-five (155) parasite positive children were treated under direct observation with dihydroartemisinin-piperaquine (DP). Gametocyte carriage was determined by microscopy seven days prior to treatment, day 0 before treatment, and on days 7, 14 and 21 post initiation of treatment.
RESULTS
The prevalence of microscopically-detectable gametocytes at screening (day -7) and enrolment (day 0) were 9% (25/274) and 13.6% (21/155) respectively. Following DP treatment, gametocyte carriage dropped to 4% (6/135), 3% (5/135) and 6% (10/151) on days 7, 14 and 21 respectively. Asexual parasites persisted in a minority of treated children, resulting in microscopically detectable parasites on days 7 (9%, 12/135), 14 (4%, 5/135) and 21 (7%, 10/151). Gametocyte carriage was inversely correlated with the age of the participants ( = 0.05) and asexual parasite density ( = 0.08). In a variate analysis, persistent gametocytaemia 7 or more days after treatment was significantly associated with post-treatment asexual parasitaemia at day 7 ( = 0.027) and presence of gametocytes on the day of treatment ( < 0.001).
CONCLUSIONS
Though DP provides both excellent cure rates for clinical malaria and a long prophylactic half-life, our findings suggest that after treatment of asymptomatic infections, both asexual parasites and gametocytes may persist in a minority of individuals during the first 3 weeks after treatment. This indicates DP may be unsuitable for use in mass drug administration strategies towards malaria elimination in Africa.
PubMed: 36860282
DOI: 10.1016/j.parepi.2023.e00292 -
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 -
Clinical Infectious Diseases : An... Oct 2021Clostridioides difficile infections (CDIs) are among the most prevalent hospital-associated infections (HAIs), particularly for intensive care unit (ICU) patients. The...
BACKGROUND
Clostridioides difficile infections (CDIs) are among the most prevalent hospital-associated infections (HAIs), particularly for intensive care unit (ICU) patients. The risks for developing active CDI from asymptomatic carriage of C. difficile are not well understood.
METHODS
We identified asymptomatic C. difficile carriage among 1897 ICU patients using rectal swabs from an existing ICU vancomycin-resistant enterococci (VRE) surveillance program. C. difficile isolates from VRE swabs, and from C. difficile-positive stool samples, were genome sequenced. Spatial-temporal data from hospital records assessed genomically identified clusters for potential transmission events.
RESULTS
Genomic analyses identified a diverse set of strains in infected patients and asymptomatic carriers. A total of 7.4% of ICU patients asymptomatically carried C. difficile; 69% of isolates carried an intact toxin locus. In contrast, 96% of C. difficile stool isolates were toxin encoding. CDI rates in asymptomatic carriers of toxin-encoding strains were 5.3% versus 0.57% in noncarriers. The relative risk for CDI with asymptomatic carriage of a toxin-encoding strain was 9.32 (95% confidence interval, 3.25-26.7). Genomic identification of clonal clusters supported analyses for asymptomatic transmission events, with spatial-temporal overlaps identified in 13 of 28 cases.
CONCLUSIONS
Our studies provide the first genomically confirmed assessments of CDI relative risk from asymptomatic carriage of toxin-encoding strains and highlight the complex dynamics of asymptomatic transmission in ICUs. Asymptomatic carriers are an active reservoir of C. difficile in the nosocomial environment. C. difficile screening can be implemented within existing HAI surveillance programs and has the potential to support infection-control efforts against this pathogen.
Topics: Clostridioides; Clostridioides difficile; Clostridium Infections; Genomics; Humans; Intensive Care Units; Risk
PubMed: 32676661
DOI: 10.1093/cid/ciaa894 -
Mathematical Biosciences and...In this paper, we consider a compartmental SIRS epidemic model with asymptomatic infection and seasonal succession, which is a periodic discontinuous differential...
In this paper, we consider a compartmental SIRS epidemic model with asymptomatic infection and seasonal succession, which is a periodic discontinuous differential system. The basic reproduction number R0 is defined and evaluated directly for this model, and uniform persistence of the disease and threshold dynamics are obtained. Specially, global dynamics of the model without seasonal force are studied. It is shown that the model has only a disease-free equilibrium which is globally stable if R0 ≤ 1, and as R0 > 1 the disease-free equilibrium is unstable and there is an endemic equilibrium, which is globally stable if the recovering rates of asymptomatic infectives and symptomatic infectives are close. These theoretical results provide an intuitive basis for understanding that the asymptomatically infective individuals and the seasonal disease transmission promote the evolution of the epidemic, which allow us to predict the outcomes of control strategies during the course of the epidemic.
Topics: Algorithms; Asymptomatic Infections; Basic Reproduction Number; Epidemics; Humans; Infections; Infectious Disease Medicine; Influenza, Human; Models, Theoretical; Seasons
PubMed: 29161868
DOI: 10.3934/mbe.2017073 -
Nature Medicine Oct 2023Despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States. Current...
Despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States. Current prevention strategies are limited by their failure to account for patients who carry C. difficile asymptomatically, who may act as hidden reservoirs transmitting infections to other patients. To improve the understanding of asymptomatic carriers' contribution to C. difficile spread, we conducted admission and daily longitudinal culture-based screening for C. difficile in a US-based intensive care unit over nine months and performed whole-genome sequencing on all recovered isolates. Despite a high burden of carriage, with 9.3% of admissions having toxigenic C. difficile detected in at least one sample, only 1% of patients culturing negative on admission to the unit acquired C. difficile via cross-transmission. While patients who carried toxigenic C. difficile on admission posed minimal risk to others, they themselves had a 24-times greater risk for developing a healthcare-onset C. difficile infection than noncarriers. Together, these findings suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of C. difficile, and that decreasing C. difficile infections in hospitals further will require interventions targeting the transition from asymptomatic carriage to infection.
Topics: Humans; United States; Clostridioides difficile; Clostridioides; Clostridium Infections; Genomics; Intensive Care Units
PubMed: 37723252
DOI: 10.1038/s41591-023-02549-4 -
Presse Medicale (Paris, France : 1983) Dec 2011Subclinical thyroid diseases are biologically defined: thyrotropin (TSH) decreased or increased with normal thyroid hormone concentrations. They are most often... (Review)
Review
Subclinical thyroid diseases are biologically defined: thyrotropin (TSH) decreased or increased with normal thyroid hormone concentrations. They are most often asymptomatics but carry a risk of long-term complications which can justify, in some cases, a treatment. The main complication of subclinical hyperthyroidism is atrial fibrillation, in particular after 60. Even if there is no controlled clinical trial available, treatment (usually with radioiodine) can be proposed to elderly subjects with autonomous thyroid disease (toxic adenoma or multinodular goitre) and TSH persistently below 0.1 mU/L. Subclinical hypothyroidism may be associated, particularly in subjects under 60, to a multifactorial increase of cardiovascular risk. An increase of TSH beyond 10 mU/L and positivity of antiTPO antibodies are the best predictors of the evolution toward overt hypothyroidism. In the elderly, there is no evidence of a risk associated with moderately increased TSH and treatment is probably not justified in most cases.
Topics: Asymptomatic Diseases; Diagnostic Techniques, Endocrine; Disease Progression; Humans; Hypothyroidism; Reference Standards; Thyroid Diseases; Thyroid Function Tests; Thyrotoxicosis
PubMed: 22115677
DOI: 10.1016/j.lpm.2011.09.009 -
Nature Communications Feb 2021Malaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of...
Malaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of their contribution to transmission in natural settings is not known. We assess the contribution of asymptomatic malaria to onward transmission using a 14-month longitudinal cohort of 239 participants in a high transmission site in Western Kenya. We identify P. falciparum in asymptomatically- and symptomatically-infected participants and naturally-fed mosquitoes from their households, genotype all parasites using deep sequencing of the parasite genes pfama1 and pfcsp, and use haplotypes to infer participant-to-mosquito transmission through a probabilistic model. In 1,242 infections (1,039 in people and 203 in mosquitoes), we observe 229 (pfcsp) and 348 (pfama1) unique parasite haplotypes. Using these to link human and mosquito infections, compared with symptomatic infections, asymptomatic infections more than double the odds of transmission to a mosquito among people with both infection types (Odds Ratio: 2.56; 95% Confidence Interval (CI): 1.36-4.81) and among all participants (OR 2.66; 95% CI: 2.05-3.47). Overall, 94.6% (95% CI: 93.1-95.8%) of mosquito infections likely resulted from asymptomatic infections. In high transmission areas, asymptomatic infections are the major contributor to mosquito infections and may be targeted as a component of transmission reduction.
Topics: Adult; Animals; Anopheles; Asymptomatic Infections; Cohort Studies; Female; Genotype; Humans; Kenya; Longitudinal Studies; Malaria, Falciparum; Male; Mosquito Vectors; Plasmodium falciparum
PubMed: 33568678
DOI: 10.1038/s41467-021-21269-2 -
Infection, Genetics and Evolution :... Apr 2021Norovirus (NoV) is the leading cause of nonbacterial foodborne outbreaks of gastroenteritis. Individuals who are asymptomatically infected may act as reservoirs to...
Norovirus (NoV) is the leading cause of nonbacterial foodborne outbreaks of gastroenteritis. Individuals who are asymptomatically infected may act as reservoirs to facilitate transmission of NoV. This retrospective study was conducted to identify the viral agent and investigate potential transmission of NoV infection in a foreigner patient who had severe acute gastroenteritis after having a meal in a restaurant in Chiang Mai province, Thailand. The fecal specimens collected from the patient and 26 restaurant staffs were tested for the presence of gastroenteritis viruses by PCR and RT-PCR. The NoV positive cases were confirmed by real-time PCR and IC kits. The sensitivity of detection of IC kit B, as compared to those of real-time PCR, could detect the viral load down to at least 2.1 × 10 copies/g of stool. The diarrheic patient was infected solely with GII.3 NoV without co-infection with any other gastroenteritis viruses while 4 staffs (15.4%) were positive for different NoV strains (3 with GII.4 and 1 with GII.17) and all were asymptomatic. Interestingly, the GII.3 NoV strain detected in fecal sample of the patient was closely related to GII.3 NoV strains detected previously in fecal samples of children hospitalized with acute diarrhea in Chiang Mai, in the same year and the same geographical area where the patient was infected, suggesting the circulation and transmission of GII.3 NoV in this area. In conclusion, our data indicated that the patient was infected with GII.3 NoV and the virus was not directly transmitted to the patient by asymptomatic food handlers instead it might be transmitted by consumption of NoV-contaminated food provided by the restaurant. In addition, the existence of NoV in asymptomatic food handlers could be a potential source of NoV transmission. Therefore, strict adherence to hand hygiene practices should be reinforced to prevent foodborne outbreaks.
Topics: Caliciviridae Infections; Carrier State; Food Handling; Gastroenteritis; Genes, Viral; Humans; Norovirus; Real-Time Polymerase Chain Reaction; Thailand
PubMed: 33465494
DOI: 10.1016/j.meegid.2021.104725 -
PLoS Neglected Tropical Diseases Jun 2022Visceral leishmaniasis (VL) remains an important infectious disease worldwide. VL-HIV coinfected individuals can present with atypical clinical forms of VL and have a... (Comparative Study)
Comparative Study
BACKGROUND
Visceral leishmaniasis (VL) remains an important infectious disease worldwide. VL-HIV coinfected individuals can present with atypical clinical forms of VL and have a high risk of VL relapse. Some cytokines have been described as potential markers to diagnose active VL and to predict the severity of the cases. However, few studies have included VL-HIV coinfected patients. We aimed to characterize the levels of several cytokines among VL-HIV coinfected individuals living in a VL-endemic area in Northeast Brazil.
METHODS
This was a retrospective, cross-sectional study, aiming to estimate the levels of various cytokines in symptomatic and asymptomatic VL-HIV coinfected individuals. There were 134 study participants (35 symptomatic VL-HIV, 75 asymptomatic VL-HIV, and 24 healthy controls), all ≥ 18 years-old. Serum cytokine levels (interferon-γ, tumor necrosis factor, and interleukins 2, 4, 6, 10, and 17A) were quantified using the Becton Dickinson-BD's Cytometric Bead Array (CBA) system.
RESULTS
The population mainly consisted of men (64.9%), with a median age of 35 (27-41) years. Asymptomatic individuals were younger (p = 0.013), with more years of education (p < 0.001), and were more often on antiretroviral therapy (p < 0.001) than those in the symptomatic group. Hemoglobin levels (p < 0.001), lymphocytes (p < 0.001) and CD4 count (p < 0.001) were lower in symptomatic individuals, while HIV viral loads were higher (p < 0.001). In the symptomatic VL-HIV coinfected group, we observed increased serum levels of IL-17A, IL-6, and IL-10 compared to asymptomatic patients and the healthy controls. There were no differences in the levels of all cytokines between asymptomatic VL-HIV coinfected individuals and the healthy controls.
CONCLUSIONS
Higher serum levels of IL-17A, IL-6, and IL-10 cytokines were observed in symptomatic coinfected individuals but not in asymptomatically infected individuals. More studies among HIV-positive persons are needed to better understand the role of serum cytokines for prognosis, to define cure and predict VL relapses in VL-HIV coinfected individuals.
Topics: Adolescent; Adult; Brazil; Coinfection; Cross-Sectional Studies; Cytokines; HIV Infections; Humans; Interleukin-10; Interleukin-17; Interleukin-6; Leishmania; Leishmaniasis, Visceral; Male; Retrospective Studies
PubMed: 35714136
DOI: 10.1371/journal.pntd.0010542 -
Journal of Clinical Epidemiology Nov 2021To characterize asymptomatic SARS-CoV-2 infections and develop a symptom-based risk score useful in primary healthcare.
OBJECTIVES
To characterize asymptomatic SARS-CoV-2 infections and develop a symptom-based risk score useful in primary healthcare.
STUDY DESIGN AND SETTING
Sixty-one thousand ninty-two community-dwelling participants in a nationwide population-based serosurvey completed a questionnaire on COVID-19 symptoms and received an immunoassay for SARS-CoV-2 IgG antibodies between April 27 and June 22, 2020. Standardized prevalence ratios for asymptomatic infection were estimated across participant characteristics. We constructed a symptom-based risk score and evaluated its ability to predict SARS-CoV-2 infection.
RESULTS
Of all, 28.7% of infections were asymptomatic (95% CI 26.1-31.4%). Standardized asymptomatic prevalence ratios were 1.19 (1.02-1.40) for men vs. women, 1.82 (1.33-2.50) and 1.45 (0.96-2.18) for individuals <20 and ≥80 years vs. those aged 40-59, 1.27 (1.03-1.55) for smokers vs. nonsmokers, and 1.91 (1.59-2.29) for individuals without vs. with case contact. In symptomatic population, a symptom-based score (weights: severe tiredness = 1; absence of sore throat = 1; fever = 2; anosmia/ageusia = 5) reached standardized seroprevalence ratio of 8.71 (7.37-10.3), discrimination index of 0.79 (0.77-0.81), and sensitivity and specificity of 71.4% (68.1-74.4%) and 74.2% (73.1-75.2%) for a score ≥3.
CONCLUSION
The presence of anosmia/ageusia, fever with severe tiredness, or fever without sore throat should serve to suspect COVID-19 in areas with active viral circulation. The proportion of asymptomatics in children and adolescents challenges infection control.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Infections; COVID-19; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Primary Health Care; Risk Factors; Seroepidemiologic Studies; Spain; Young Adult
PubMed: 34126206
DOI: 10.1016/j.jclinepi.2021.06.005