Population-based studies conducted in Latin America have shown a high proportion of asymptomatic and submicroscopic malarial infections. Considering efforts aiming at regional elimination, it is ...important to investigate the role of this asymptomatic reservoir in malaria transmission in peri-urban areas. This study aimed to estimate the prevalence of Plasmodium spp. and gametocyte burden on symptomatic and asymptomatic infections in the Brazilian Amazon.
Two cross-sectional household surveys (CS) were conducted including all inhabitants in a peri-urban area of Manaus, western Amazonas State, Brazil. Malaria parasites were detected by light microscopy (LM) and qPCR. Sexual stages of Plasmodium spp. were detected by LM and RT-qPCR. A total of 4083 participants were enrolled during the two surveys. In CS1, the prevalence of Plasmodium vivax infections was 4.3% (86/2010) by qPCR and 1.6% (32/2010) by LM. Fifty percent (43/86) of P. vivax infected individuals (qPCR) carried P. vivax gametocytes. In CS2, 3.4% (70/2073) of participants had qPCR-detectable P. vivax infections, of which 42.9% (30/70) of infections were gametocyte positive. The P. vivax parasite density was associated with gametocyte carriage (P < 0.001). Sixty-seven percent of P. vivax infected individuals and 53.4% of P. vivax gametocyte carriers were asymptomatic.
This study confirms a substantial proportion of asymptomatic and submicroscopic P. vivax infections in the study area. Most asymptomatic individuals carried gametocytes and presented low asexual parasitemia. This reservoir actively contributes to malaria transmission in the Brazilian Amazon, underscoring a need to implement more efficient control and elimination strategies.
Abstract
Background
Relapses in vivax malaria have posed great challenges for malaria control, and they also account for a great proportion of reported cases. Knowing the real effectiveness of a ...7-day primaquine (PQ) scheme is crucial in order to evaluate not only the cost-effectiveness of implementing new anti-hypnozoite drugs, but also how health education strategies can guarantee better compliance and be reinforced. This study aimed to evaluate the effect of daily treatment with chloroquine and PQ supervised by health workers
versus
prescription without supervision.
Methods
The outcome was the passive detection of new positive thick blood smears up to 180 days, based on the official data records from the National Malaria Control Programme. The recurrences seen in the real life were, therefore, used as a surrogate for true relapses.
Results
Patients under supervised treatment had a lower risk of recurrence up to day 180 when compared to the unsupervised treatment (17.9%
vs.
36.1%;
p
= 0.027).
Conclusions
The lack of supervision in the non-supervised group (which followed standard of care in the real life) enabled proper comparison, as consent itself would have lead to greater compliance in this group. Future studies should scale such an analysis to different settings in the Brazilian Amazon.
As quantitative glucose 6-phosphate dehydrogenase deficiency (G6PDd) screening tools are evaluated in operational studies, questions remain as to whether they are cost-effective. Here, a ...cost-effectiveness analysis (CEA) was performed to estimate the Incremental Cost-effectiveness Ratio (ICER) of the introduction of quantitative screening test to detect G6PDd among P. vivax carriers in two municipalities in the Brazilian Amazon.
This cost-effectiveness analysis evaluated the use of the Standard G6PD quantitative screening test in vivax malaria treatment units in two municipalities of the Brazilian Amazon. Using the perspective of the Brazilian public health system, the analysis was performed for the outcome 'PQ-associated hospitalization avoided', based on a decision tree model. The results indicated that the G6PDd screening strategy compared with the routine strategy was highly cost-effective, with an ICER of US$495 per additional hospitalization avoided, which represented less than 8% of one Brazilian gross domestic product per capita (US$6,822). The uncertainties evaluated in the sensitivity analysis did not significantly affect the ICER identified in the base-case.
This cost-effectiveness analysis showed the quantitative G6PD testing was effective in avoiding PQ-associated hospitalizations. The incorporation of G6PD screening is of paramount importance towards P. vivax malaria elimination in the Amazon to promote the safe use of primaquine and tafenoquine.
In recent years, considerable success in reducing its incidence has been achieved in Brazil, leading to a relative increase in the proportion of cases caused by Plasmodium vivax, considered a ...harder-to-eliminate parasite. This study aim is to describe the transmission dynamics and associated risk factors in a rural settlement area in the Western Brazilian Amazon.
A prospective cohort was established in a rural settlement area for 3 years. Follow-up included continuous passive case detection and monthly active case detection for a period of 6 months. Demographic, clinical and transmission control practices data were collected. Malaria diagnosis was performed through thick blood smear. Univariable and multivariable analyses of factors associated with malaria incidence were performed using negative binomial regression models. Factors associated with recurrence of P. vivax and Plasmodium falciparum malaria within 90 days of a previous episode were analysed using univariable and multivariable Cox-Proportional Hazard models.
Malaria prevalence decreased from 7 % at the study beginning to 0.6 % at month 24, with P. vivax predominating and P. falciparum disappearing after 1 year of follow-up. Malaria incidence was significantly higher in the dry season IRR (95 % CI) 1.4 (1.1-1.6); p < 0.001). Use of ITN was associated to malaria protection in the localities IRR (95 % CI) 0.7 (0.6-0.8); p = 0.001). A recurrent P. vivax episode within 90 days was observed in 29.4 % of individuals after an initial diagnosis. A previous P. vivax IRR (95 % CI) 2.3 (1.3-4.0); p = 0.006) or mixed P. vivax + P. falciparum IRR (95 % CI) 2.9 (1.5-5.7); p = 0.002) infections were significantly associated to a vivax malaria episode within 90 days of follow-up.
In an area of P. falciparum and P. vivax co-endemicity, a virtual disappearance of P. falciparum was observed with P. vivax increasing its relative contribution, with a large proportion of recurring episodes. This finding reinforces the perception of P. falciparum being more responsive to early diagnosis and treatment and ITN use and the contribution of relapsing P. vivax to maintain this species' transmission. In areas of P. vivax endemicity, antihypnozoite treatment effectiveness assessment in different transmission intensity may be a fundamental activity for malaria control and elimination.
There is a growing body of evidence linking micronutrient deficiencies and malaria incidence arising mostly from P. falciparum endemic areas. We assessed the impact of micronutrient deficiencies on ...malaria incidence and vice versa in the Brazilian state of Amazonas.
We evaluated children <10 years old living in rural communities in the state of Amazonas, Brazil, from May 2010 to May 2011. All children were assessed for sociodemographic, anthropometric and laboratory parameters, including vitamin A, beta-carotene, zinc and iron serum levels at the beginning of the study (May 2010) and one year later (May 2011). Children were followed in between using passive surveillance for detection of symptomatic malaria. Those living in the study area at the completion of the observation period were reassessed for micronutrient levels. Univariate Cox-proportional Hazards models were used to assess whether micronutrient deficiencies had an impact on time to first P. vivax malaria episode. We included 95 children median age 4.8 years (interquartile range IQR: 2.3-6.6), mostly males (60.0%) and with high maternal illiteracy (72.6%). Vitamin A deficiencies were found in 36% of children, beta-carotene deficiency in 63%, zinc deficiency in 61% and iron deficiency in 51%. Most children (80%) had at least one intestinal parasite. During follow-up, 16 cases of vivax malaria were diagnosed amongst 13 individuals. Micronutrient deficiencies were not associated with increased malaria incidence: vitamin A deficiency Hazard ratio (HR): 1.51; P-value: 0.45; beta-carotene HR: 0.47; P-value: 0.19; zinc HR: 1.41; P-value: 0.57 and iron HR: 2.31; P-value: 0.16). Upon reevaluation, children with al least one episode of malaria did not present significant changes in micronutrient levels.
Micronutrient serum levels were not associated with a higher malaria incidence nor the malaria episode influenced micronutrient levels. Future studies targeting larger populations to assess micronutrients levels in P. vivax endemic areas are warranted in order to validate these results.
Although primaquine (PQ) is indicated for G6PD-deficient patients, data on weekly PQ use in Brazil are limited.
We aimed to investigate malaria recurrences among participants receiving daily and ...weekly PQ treatments in a real-life setting of two municipalities in the Amazon between 2019 and 2020.
Patients receiving weekly PQ treatment had a lower risk of recurrence than those receiving daily PQ treatment (risk ratio: 0.62, 95% confidence interval: 0.41-0.94), using a model adjusted for study site.
Weekly PQ use did not increase the risk of malaria recurrence. Further studies with larger populations are warranted.
Plasmodium vivax malaria (Pv-malaria) is still considered a neglected disease despite an alarming number of individuals being infected annually. Malaria pathogenesis occurs with the onset of the ...vector-parasite-host interaction through the binding of pathogen-associated molecular patterns (PAMPs) and receptors of innate immunity, such as toll-like receptors (TLRs). The triggering of the signaling cascade produces an elevated inflammatory response. Genetic polymorphisms in TLRs are involved in susceptibility or resistance to infection, and the identification of genes involved with Pv-malaria response is important to elucidate the pathogenesis of the disease and may contribute to the formulation of control and elimination tools.
A retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the state of Amazonas, Brazil. Genetic polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 325 patients infected with P. vivax and 274 healthy individuals without malaria history in the prior 12 months from the same endemic area. Parasite load was determined by qPCR. Simple and multiple logistic/linear regressions were performed to investigate association between the polymorphisms and the occurrence of Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T (TLR9 -1486C/T) genotypes appear to be risk factors for infection by P. vivax (TLR5: C/C vs. C/T OR: 2.116, 95% CI: 1.054-4.452, p = 0.031; TLR9: C/C vs. T/T OR: 1.919, 95% CI: 1.159-3.177, p = 0.010; respectively). Fever (COEF = 7599.46, 95% CI = 3063.80-12135.12, p = 0.001) and the C/C genotype of TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83-30540.44, p = 0.014) were independently associated with increased parasitemia in patients with Pv-malaria.
Variants of TLRs may predispose individuals to infection by P. vivax. The TLR5 R392StopCodon and TLR9 -1486C/T variants are associated with susceptibility to Pv-malaria. Furthermore, the TLR9 variant -1237C/C correlates with high parasitemia.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not routinely performed before primaquine treatment in most
endemic areas, despite the risk of primaquine-associated hemolysis. This is ...due to the operational challenges associated with pragmatic G6PD testing and as such needs to be addressed.
This mixed-methods operational study was aimed at implementing the quantitative point-of-care Standard
G6PD (SD Biosensor, Korea) screening test in malaria treatment units (MTUs) in the municipalities of Rio Preto da Eva and Mâncio Lima, in the Brazilian Amazon, between mid-January 2020 and December 2020. In total, 1286
cases were treated based on the Standard G6PD test: 1230 had activity equal to or greater than 4.0 U/g Hb, and 56 less than 4.0 U/g Hb. No G6PD deficient (G6PDd) genotypes were found in 96 samples from the 1230, and only 21 of the 56 G6PDd cases had confirmed G6PDd genotypes. Evaluations were conducted on the proficiency of health care professionals (HCPs) training to perform the test, the reliability of testing performed in the field, and the perceptions of HCPs and patients about the implementation. Post-training proficiency was 73.4% after a 4-hour training session. This study revealed that locations with lower malaria caseloads will need regular refresher training. The test was well accepted by both HCPs and patients. Signs and symptoms of hemolysis were not always associated with malaria treatment drugs by HCPs and patients.
Point-of-care quantitative G6PD testing can be performed at MTUs in the Brazilian Amazon to inform treatment decisions with primaquine. Limitations related to technical and cultural aspects need to be addressed further when expanding screening to larger areas.
Plasmodium vivax is responsible for a significant proportion of malaria cases worldwide and is increasingly reported as a cause of severe disease. The objective of this study was to characterize ...severe vivax disease among children hospitalized in intensive care units (ICUs) in the Western Brazilian Amazon, and to identify risk factors associated with disease severity.
In this retrospective study, clinical records of 34 children, 0-14 years of age hospitalized in the 11 public pediatric and neonatal ICUs of the Manaus area, were reviewed. P. falciparum monoinfection or P. falciparum/P. vivax mixed infection was diagnosed by microscopy in 10 cases, while P. vivax monoinfection was confirmed in the remaining 24 cases. Two of the 24 patients with P. vivax monoinfection died. Respiratory distress, shock and severe anemia were the most frequent complications associated with P. vivax infection. Ninety-one children hospitalized with P. vivax monoinfections but not requiring ICU were consecutively recruited in a tertiary care hospital for infectious diseases to serve as a reference population (comparators). Male sex (p = 0.039), age less than five years (p = 0.028), parasitemia greater than 500/mm(3) (p = 0.018), and the presence of any acute (p = 0.023) or chronic (p = 0.017) co-morbidity were independently associated with ICU admission. At least one of the WHO severity criteria for malaria (formerly validated for P. falciparum) was present in 23/24 (95.8%) of the patients admitted to the ICU and in 17/91 (18.7%) of controls, making these criteria a good predictor of ICU admission (p = 0.001). The only investigated criterion not associated with ICU admission was hyperbilirubinemia (p = 0.513).
Our study points to the importance of P. vivax-associated severe disease in children, causing 72.5% of the malaria admissions to pediatric ICUs. WHO severity criteria demonstrated good sensitivity in predicting severe P. vivax infection in this small case series.
Chronic classical music was reported to increase parasympathetic activitywhen evaluating heart rate variability (HRV). It is poor in the literature investigation of the acute effects of baroque and ...heavy metal styles of musical auditory stimulation on HRV. In this study we evaluated the acute effects of relaxant baroque and excitatory heavy metal music on the geometric indices of HRV in healthy men.
The study was performed in 12 healthy men between 18 and 30 years old. We excluded persons with previous experience with music instrument and those who had affinity with the song styles. We analyzed the following indices: RRtri, TINN and Poincaré plot (SD1, SD2 and SD1/SD2 ratio). HRV was recorded at rest for ten minutes. Subsequently they were exposed to relaxant baroque or excitatory heavy metal music for five minutes through an earphone. After the first music exposure they remained at rest for more five minutes and them they were exposed again to Baroque or Heavy Metal music (65-80 dB). The sequence of songs was randomized for each individual.
The RRTri and SD2 indices were reduced during the heavy metal musical auditory stimulation (p < 0.05). No changes were observed regarding TINN, SD1 and SD1/SD2 ratio (p > 0.05).The qualitative Poincaré plot analysis indicated that during relaxant classical baroque music there was observed a higher beat-to-beat dispersion of RR intervals compared with no music exposure and during excitatory heavy metal musical auditory stimulation, showing higher HRV.
We suggest that excitatory heavy metal music acutely decreases global HRV.
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