Comprehensive analysis of right fascicular and right bundle branch blocks: A multi-center study.

Electrocardiographic patterns of right bundle branch and fascicular blocks were comprehensively analyzed in a two-phase study. The research aimed to address the scarcity of literature and the absence of standardized diagnostic criteria for these conditions. It revealed a weak correlation between the cardiac axis and age and highlighted the high misdiagnosis rate of these blocks. Furthermore, it discussed the challenges in fulfilling existing diagnostic criteria. The study emphasizes the need for a more precise understanding of right ventricular conduction disorders and the importance of developing robust diagnostic criteria.

The landscape of drug resistance in Plasmodium falciparum malaria in the Democratic Republic of Congo: a mapping systematic review.

CONTEXT: The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country. METHODS: A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science). RESULTS: We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine-pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN-GE mutants (i.e., parasites carrying the PfDHFR N51I-C59R-S108N and PfDHPS A437G-K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates. CONCLUSIONS: Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.

Right fascicular blocks: A case series and a comprehensive electrocardiographic analysis.

The main trunk of the right bundle branch divides into an anterior, middle (lateral) and posterior fascicle. This article describes the right anterior and posterior fascicular block. They present a diagnostic challenge and are often overlooked during diagnostic processes. The studied patients were young adults whose electrocardiographic tracings were registered at the Mexican Faculty of Medicine of La Salle University. The presence of delayed R-peak time in aVR and V1, along with the described ventricular complex morphologies, and a right or left deviation of the cardiac axis exceeding +60°, may be suggestive of right fascicular blocks.

Osificación heterotópica tras artroplastia de cadera: papel de la gammagrafía SPECT/TC ósea / Heterotopic ossification after hip arthroplasty: role of bone SPECT/CT scintigraphy

La osificación heterotópica es una condición limitante, que afecta predominantemente a la cadera. Dada su relación con patología postraumática/posquirúrgica, la gammagrafía ósea SPECT/TC resulta de especial utilidad en el diagnóstico diferencial con movilización protésica, aun cuando no hay alteraciones radiológicas. Además, resulta ser una herramienta eficaz para planificación quirúrgica atendiendo al grado de maduración ósea y la posibilidad de fabricar biomodelos mediante impresión 3D.(AU)

Heterotopic ossification is a limiting condition that predominantly affects the hip. Because of its association with post-trau-matic/postoperative pathology, bone SPECT/CT scintigraphy has proven to be especially useful regarding differential diag-nosis involving prosthetic mobilization, even in the absence of radiological abnormalities. Additionally, it is an effective toolfor surgical planning, considering the degree of bone maturation and the possibility of creating biomodels using 3Dprinting.(AU)

Reduced polymorphism of Plasmodium vivax early transcribed membrane protein (PvETRAMP) 11.2.

BACKGROUND: ETRAMP11.2 (PVX_003565) is a well-characterized protein with antigenic potential. It is considered to be a serological marker for diagnostic tools, and it has been suggested as a potential vaccine candidate. Despite its immunological relevance, the polymorphism of the P. vivax ETRAMP11.2 gene (pvetramp11.2) remains undefined. The genetic variability of an antigen may limit the effectiveness of its application as a serological surveillance tool and in vaccine development and, therefore, the aim of this study was to investigate the genetic diversity of pvetramp11.2 in parasite populations from Amazonian regions and worldwide. We also evaluated amino acid polymorphism on predicted B-cell epitopes. The low variability of the sequence encoding PvETRAMP11.2 protein suggests that it would be a suitable marker in prospective serodiagnostic assays for surveillance strategies or in vaccine design against P. vivax malaria. METHODS: The pvetramp11.2 of P. vivax isolates collected from Brazil (n = 68) and Peru (n = 36) were sequenced and analyzed to assess nucleotide polymorphisms, allele distributions, population differentiation, genetic diversity and signature of selection. In addition, sequences (n = 104) of seven populations from different geographical regions were retrieved from the PlasmoDB database and included in the analysis to study the worldwide allele distribution. Potential linear B-cell epitopes and their polymorphisms were also explored. RESULTS: The multiple alignments of 208 pvetramp11.2 sequences revealed a low polymorphism and a marked geographical variation in allele diversity. Seven polymorphic sites and 11 alleles were identified. All of the alleles were detected in isolates from the Latin American region and five alleles were detected in isolates from the Southeast Asia/Papua New Guinea (SEA/PNG) region. Three alleles were shared by all Latin American populations (H1, H6 and H7). The H1 allele (reference allele from Salvador-1 strain), which was absent in the SEA/PNG populations, was the most represented allele in populations from Brazil (54%) and was also detected at high frequencies in populations from all other Latin America countries (range: 13.0% to 33.3%). The H2 allele was the major allele in SEA/PNG populations, but was poorly represented in Latin America populations (only in Brazil: 7.3%). Plasmodium vivax populations from Latin America showed a marked inter-population genetic differentiation (fixation index [Fst]) in contrast to SEA/PNG populations. Codon bias measures (effective number of codons [ENC] and Codon bias index [CBI]) indicated preferential use of synonymous codons, suggesting selective pressure at the translation level. Only three amino acid substitutions, located in the C-terminus, were detected. Linear B-cell epitope mapping predicted two epitopes in the Sal-1 PvETRAMP11.2 protein, one of which was fully conserved in all of the parasite populations analyzed. CONCLUSIONS: We provide an overview of the allele distribution and genetic differentiation of ETRAMP11.2 antigen in P. vivax populations from different endemic areas of the world. The reduced polymorphism and the high degree of protein conservation supports the application of PvETRAMP11.2 protein as a reliable antigen for application in serological assays or vaccine design. Our findings provide useful information that can be used to inform future study designs.

Diagnostic relevance of 2-[18 F]-FDG PET/CT in patients recently diagnosed with monoclonal gammopathy of undetermined significance.

2-[18 F]-FDG PET/CT is a useful diagnostic technique to assess bone and soft tissue disease in multiple myeloma (MM) but is not recommended by the International Myeloma Working Group for the evaluation of monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to evaluate the role of 2-[18 F]-FDG PET/CT in the management of these patients. An observational retrospective study was conducted on 338 patients with MGUS who underwent 2-[18 F]-FDG PET/CT. The mean age was 70.80 ± 11.84 years, and 69.2% of patients had cardiovascular risk factors. Patients were classified according to their progression risk (Mayo Clinic). The mean post-diagnosis follow-up was 8.35 ± 14.46 months. Pathological findings were recorded in 49 patients: 30 with myeloma bone lesions (15 in the initial study and 15 in follow-up) and 19 with other neoplastic (n = 13) or pathologically significant findings (n = 6). Body mass index, monoclonal component rate (MCR) > 1 g/dL and ≥1 risk factors for MM were significant in univariate logistic regression analyses. The MCR emerged as the main predictor of a positive 2-[18 F]-FDG PET/CT in adjusted multivariate regression analysis, with an area under the receiver operating characteristic curve of 0.785 and cutoff for optimal sensitivity/specificity of 1.0 ng/mL (71.4% sensitivity, 71.2% specificity). 2-[18 F]-FDG PET/CT results correctly classify patients with MGUS and could improve the detection of bone lesions over existing techniques, with the additional possibility of detecting neoplastic processes. The best parameter to predict a positive 2-[18 F]-FDG PET/CT was the MCR.

[Assessment of pulmonary embolism related to active SARS-CoV-2 infection in pregnant women.] / Valoración del tromboembolismo pulmonar relacionado con infección SARS-CoV-2 activa en pacientes embarazadas.

AIM: To analyze the sample of pregnant patients who underwent pulmonary perfusion scintigraphy to rule out the pulmonary embolism (PE) suspicion during the acute COVID-19 infection hospitalization period in our hospital. MATERIAL AND METHODS: SPECT scintigraphy with a reduced dose (111 MBq) of 99mTc-macroaggregated albumin was performed in all of the patients (n=5). The obtained images were interpreted by comparing the findings with the radiological images according to the PISAPED criteria. RESULTS: Only one of the 5 patients was diagnosed with PE. Two patients obtained pathological findings of the scintigraphy attributable to radiological alterations due to COVID-19 pneumonia, and the other two had normal pulmonary perfussion. CONCLUSION: Given the non-specific features of the clinical manifestations and D-dimer values in COVID-19, as well as their similarity to those of PE, the pulmonary perfusion scintigraphy plays a crucial role in the screening of PE in these patients due to its high sensitivity and lower irradiation compared to CT. Despite the limited number of patients, the results obtained have special relevance related to the absence of scientific publications on this group of patients within the context of COVID-19 pandemic exceptional situation.

Relative contribution of low-density and asymptomatic infections to Plasmodium vivax transmission in the Amazon: pooled analysis of individual participant data from population-based cross-sectional surveys.

Background: Low-density and asymptomatic Plasmodium vivax infections remain largely undetected and untreated and may contribute significantly to malaria transmission in the Amazon. Methods: We analysed individual participant data from population-based surveys that measured P vivax prevalence by microscopy and polymerase chain reaction (PCR) between 2002 and 2015 and modelled the relationship between parasite density and infectiousness to vectors using membrane feeding assay data. We estimated the proportion of sub-patent (i.e., missed by microscopy) and asymptomatic P vivax infections and examined how parasite density relates to clinical manifestations and mosquito infection in Amazonian settings. Findings: We pooled 24,986 observations from six sites in Brazil and Peru. P vivax was detected in 6·8% and 2·1% of them by PCR and microscopy, respectively. 58·5% to 92·6% of P vivax infections were asymptomatic and 61·2% to 96·3% were sub-patent across study sites. P vivax density thresholds associated with clinical symptoms were one order of magnitude higher in children than in adults. We estimate that sub-patent parasite carriers are minimally infectious and contribute 12·7% to 24·9% of the community-wide P vivax transmission, while asymptomatic carriers are the source of 28·2% to 79·2% of mosquito infections. Interpretation: Asymptomatic P vivax carriers constitute a vast infectious reservoir that, if targeted by malaria elimination strategies, could substantially reduce malaria transmission in the Amazon. Infected children may remain asymptomatic despite high parasite densities that elicit clinical manifestations in adults. Funding: US National Institutes of Health, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Belgium Development Cooperation.

Tafenoquine for the treatment of Plasmodium vivax malaria.

INTRODUCTION: Plasmodium vivax malaria causes significant disease burden worldwide, especially in Latin America, Southeast Asia, and Oceania. P. vivax is characterized by the production of liver hypnozoites that cause clinical relapses upon periodic activation. Primaquine, an 8-aminoquinoline drug, has been the standard of care for decades to treat liver-stage P. vivax malaria; however, it requires long treatment regimens (one to two weeks) that lead to poor adherence and thus clinical relapses. Tafenoquine (TFQ), a newly available and efficacious single-dose 8-aminoquinoline, aims to address this challenge. Safe administration is possible when paired with the use of glucose-6-phosphate dehydrogenase (G6PD) diagnostics to prevent 8-aminoquinoline-induced hemolysis in patients with underlying G6PD deficiency (G6PDd). AREAS COVERED: In this review, the authors present the recent literature regarding the pharmacology, efficacy, safety, and tolerability of TFQ and highlight regional differences in these areas. The authors also discuss the potential for TFQ, complemented with primaquine PQ and effective screening for G6PDd, to improve P. vivax clinical management and facilitate targeted mass drug administration in communities to decrease transmission. EXPERT OPINION: Clinical studies show therapeutic efficacy of TFQ as well as a good performance in terms of safety and tolerability. Additional research regarding the effectiveness and safety TFQ in malaria elimination strategies, such as targeted or mass drug administration, are needed.

Assessment of the diagnostic accuracy and relevance of a novel ELISA system developed for seroepidemiologic surveys of Helicobacter pylori infection in African settings.

Beside diagnostic uncertainties due to the lack of a perfect gold standard test for Helicobacter pylori infection, the diagnosis and the prevalence estimation for this infection encounter particular challenges in Africa including limited diagnostic tools and specific genetic background. We developed and evaluated the accuracy of an enzyme-linked immunosorbent assay (ELISA) system tailored for H. pylori genetics in Africa (HpAfr-ELISA). Strains belonging to main genetic populations infecting Africans were exploited as sources for whole-cell antigens to establish in-house the ELISA system. A phase II unmatched case-control study explored the diagnostic accuracy of the HpAfr-ELISA using a training set of samples collected from dyspeptic patients from Kinshasa, the Democratic Republic of Congo (DRC) who had been tested with invasive standard tests (i.e., histology, culture, and rapid urease test) in 2017. Then the assay was cross-validated through a community-based survey assessing the prevalence of H. pylori and associated factors in 425 adults from Mbujimayi, DRC in 2018. Bayesian inferences were used to deal with statistical uncertainties of estimates (true prevalence, sensitivity, and specificity) in the study population. At its optimal cut-off-value 20.2 U/mL, the assay achieved an estimated sensitivity of 97.6% (95% credible interval [95%CrI]: 89.2; 99.9%) and specificity of 90.5% (95%CrI: 78.6; 98.5). Consistent outcomes obtained at repeated tests attested the robustness of the assay (negative and positive agreements always > 70%). The true prevalence of H. pylori was estimated 53.8% [95%CrI: 42.8; 62.7%]. Increasing age (adjusted odds ratio [aOR] > 1.0 [95% confidence interval (CI): > 1.0; 1.1]; p<0.001), overcrowding households (aOR = 3.2 [95%CI: 2.0; 5.1]; p<0.001), and non-optimal hand hygiene (aOR = 4.5 [95%CI: 2.0; 11.4]; p = 0.001) were independently associated with the H. pylori-seropositivity. The novel ELISA system has demonstrated good diagnostic accuracy and potential usefulness for management and mitigation strategies for H. pylori infection in African settings.

Evaluation of the usefulness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in a context with increased resistance of Plasmodium falciparum in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo.

BACKGROUND: Increasing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) threatens its usefulness for intermittent preventive treatment in pregnancy (IPTp-SP). The prophylactic effects of IPTp-SP on maternal malaria and adverse pregnancy outcomes were evaluated in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo (DRC). METHODS: Laboring women (n = 844) and respective newborns were investigated. Blood samples collected from women were tested for malaria using rapid diagnostic test (RDT), blood smears examination, and real-time PCR. The hemoglobin level was measured by HemoCue© analyzer. A PCR-RFLP method was applied for detecting N51I, C59R, and S108N mutations on dhfr along with A437G and K540E mutations on dhps in P. falciparum positive samples. Logistic regression models assessed relationships between IPTp-SP uptake and pregnancy outcomes. RESULTS: P. falciparum malaria was detected at delivery in 10.8% of women and was statistically associated with fever during the pregnancy (OR = 2.9 [1.5; 6.3]; p = 0.004) and maternal anemia (OR = 3.9 [2.4; 6.3]; p < 0.001). One out of five parasites was a quintuple mutant encoding dhfr mutations 51I, 59R, and 108 N along with dhps mutations 437G and 540E. The molecular profile of parasites (i.e., 32.6% of parasites carrying dhps K540E) was suitable with continued use of SP for IPTp. IPTp-SP uptake was not associated with reduced maternal malaria, fever reported in pregnancy, or fetal deaths (p > 0.05). Conversely, three or more doses of SP were associated with reduced maternal anemia at delivery (OR = 0.4 [0.2; 0.9]; p = 0.024), shortened gestation (OR = 0.4 [0.2; 0.8]; p = 0.009), and low-birth weights (OR = 0.2 [0.1; 0.5]; p < 0.001). CONCLUSION: IPTp-SP was not associated with reduced maternal malaria in our study, but evidence was found of a prophylactic effect against adverse pregnancy outcomes. To counteract further loss of clinical effects of IPTp-SP in the study population, alternative strategies able to improve its anti-malarial efficacy such as combination of SP with partner molecules should be implemented.

Care-seeking behaviour and socio-economic burden associated with uncomplicated malaria in the Democratic Republic of Congo.

BACKGROUND: This study aimed to estimate the socio-economic costs of uncomplicated malaria and to explore health care-seeking behaviours that are likely to influence these costs in the Democratic Republic of Congo (DRC), a country ranked worldwide as the second most affected by malaria. METHODS: In 2017, a cross-sectional survey included patients with uncomplicated malaria in 64 healthcare facilities from 10 sentinel sites of the National Malaria Control Programme (NMCP) in the DRC. A standard questionnaire was used to assess health care-seeking behaviours of patients. Health-related quality of life (HRQL) and disutility weights (DW) of illness were evaluated by using the EuroQol Group's descriptive system (EQ-5D-3L) and its visual analogue scale (EQ VAS). Malaria costs were estimated from a patient's perspective. Probabilistic sensitivity analyses (PSA) evaluated the uncertainty around the cost estimates. Generalized regression models were fitted to assess the effect of potential predictive factors on the time lost and the DW during illness. RESULTS: In total, 1080 patients (age: 13.1 ± 14 years; M/F ratio: 1.1) were included. The average total costs amounted to US$ 36.3 [95% CI 35.5-37.2] per malaria episode, including US$ 16.7 [95% CI 16.3-17.1] as direct costs and US$ 19.6 [95% CI 18.9-20.3] indirect costs. During care seeking, economically active patients and their relatives lost respectively 3.3 ± 1.8 and 3.4 ± 2.1 working days. This time loss occurred mostly at the pre-hospital stage and was the parameter associated the most with the uncertainty around malaria cost estimates. Patients self-rated an average 0.36 ± 0.2 DW and an average 0.62 ± 0.3 EQ-5D index score per episode. A lack of health insurance coverage (896 out of 1080; 82.9%) incurred substantially higher costs, lower quality of life, and heavier DW while leading to longer time lost during illness. Residing in rural areas incurred a disproportionally higher socioeconomic burden of uncomplicated malaria with longer time lost due to illness and limited access to health insurance mechanisms. CONCLUSION: Uncomplicated malaria is associated with high economic costs of care in the DRC. Efforts to reduce the cost-of-illness should target time lost at the pre-hospital stage and social disparities in the population, while reinforcing measures for malaria control in the country.

PvMSP8 as a Novel Plasmodium vivax Malaria Sero-Marker for the Peruvian Amazon.

The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian Amazon. In a first evaluation, IgGs against PvMSP8 and PvMSP10 proteins were measured by Luminex in a cohort of 422 Amazonian individuals with known history of Pv exposure (monthly data of infection status by qPCR and/or microscopy over five months). Both serological responses were able to discriminate between exposed and non-exposed individuals in a good manner, with slightly higher performance of anti-PvMSP10 IgGs (area under the curve AUC = 0.78 [95% CI = 0.72-0.83]) than anti-PvMSP8 IgGs (AUC = 0.72 [95% CI = 0.67-0.78]) (p = 0.01). In a second evaluation, the analysis by ELISA of 1251 plasma samples, collected during a population-based cross-sectional survey, confirmed the good performance of anti-PvMSP8 IgGs for discriminating between individuals with Pv infection at the time of survey and/or with antecedent of Pv in the past month (AUC = 0.79 [95% CI = 0.74-0.83]). Anti-PvMSP8 IgG antibodies can be considered as a good biomarker of recent Pv exposure in low-moderate transmission settings of the Peruvian Amazon.

Integrating Parasitological and Entomological Observations to Understand Malaria Transmission in Riverine Villages in the Peruvian Amazon.

BACKGROUND: Remote rural riverine villages account for most of the reported malaria cases in the Peruvian Amazon. As transmission decreases due to intensive standard control efforts, malaria strategies in these villages will need to be more focused and adapted to local epidemiology. METHODS: By integrating parasitological, entomological, and environmental observations between January 2016 and June 2017, we provided an in-depth characterization of malaria transmission dynamics in 4 riverine villages of the Mazan district, Loreto department. RESULTS: Despite variation across villages, malaria prevalence by polymerase chain reaction in March 2016 was high (>25% in 3 villages), caused by Plasmodium vivax mainly and composed of mostly submicroscopic infections. Housing without complete walls was the main malaria risk factor, while households close to forest edges were more commonly identified as spatial clusters of malaria prevalence. Villages in the basin of the Mazan River had a higher density of adult Anopheles darlingi mosquitoes, and retained higher prevalence and incidence rates compared to villages in the basin of the Napo River despite test-and-treat interventions. CONCLUSIONS: High heterogeneity in malaria transmission was found across and within riverine villages, resulting from interactions between the microgeographic landscape driving diverse conditions for vector development, housing structure, and human behavior.

Temporal and Microspatial Heterogeneity in Transmission Dynamics of Coendemic Plasmodium vivax and Plasmodium falciparum in Two Rural Cohort Populations in the Peruvian Amazon.

BACKGROUND: Malaria is highly heterogeneous: its changing malaria microepidemiology needs to be addressed to support malaria elimination efforts at the regional level. METHODS: A 3-year, population-based cohort study in 2 settings in the Peruvian Amazon (Lupuna, Cahuide) followed participants by passive and active case detection from January 2013 to December 2015. Incidence and prevalence rates were estimated using microscopy and polymerase chain reaction (PCR). RESULTS: Lupuna registered 1828 infections (1708 Plasmodium vivax, 120 Plasmodium falciparum; incidence was 80.7 infections/100 person-years (95% confidence interval [CI] , 77.1-84.5). Cahuide detected 1046 infections (1024 P vivax, 20 P falciparum, 2 mixed); incidence was 40.2 infections/100 person-years (95% CI, 37.9-42.7). Recurrent P vivax infections predominated onwards from 2013. According to PCR data, submicroscopic predominated over microscopic infections, especially in periods of low transmission. The integration of parasitological, entomological, and environmental observations evidenced an intense and seasonal transmission resilient to standard control measures in Lupuna and a persistent residual transmission after severe outbreaks were intensively handled in Cahuide. CONCLUSIONS: In 2 exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.

Spatial and molecular mapping of Pfkelch13 gene polymorphism in Africa in the era of emerging Plasmodium falciparum resistance to artemisinin: a systematic review.

The spread of Plasmodium falciparum isolates carrying mutations in the kelch13 (Pfkelch13) gene associated with artemisinin resistance (PfART-R) in southeast Asia threatens malaria control and elimination efforts. Emergence of PfART-R in Africa would result in a major public health problem. In this systematic review, we investigate the frequency and spatial distribution of Pfkelch13 mutants in Africa, including mutants linked to PfART-R in southeast Asia. Seven databases were searched (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline, and Web of Science) for relevant articles about polymorphisms of the Pfkelch13 gene in Africa before January, 2019. Following PRISMA guidelines, 53 studies that sequenced the Pfkelch13 gene of 23 100 sample isolates in 41 sub-Saharan African countries were included. The Pfkelch13 sequence was highly polymorphic (292 alleles, including 255 in the Pfkelch13-propeller domain) but with mutations occurring at very low relative frequencies. Non-synonymous mutations were found in only 626 isolates (2·7%) from west, central, and east Africa. According to WHO, nine different mutations linked to PfART-R in southeast Asia (Phe446Ile, Cys469Tyr, Met476Ile, Arg515Lys, Ser522Cys, Pro553Leu, Val568Gly, Pro574Leu, and Ala675Val) were detected, mainly in east Africa. Several other Pfkelch13 mutations, such as those structurally similar to southeast Asia PfART-R mutations, were also identified, but their relevance for drug resistance is still unknown. This systematic review shows that Africa, thought to not have established PfART-R, reported resistance-related mutants in the past 5 years. Surveillance using PfART-R molecular markers can provide valuable decision-making information to sustain the effectiveness of artemisinin in Africa.

Economic costs analysis of uncomplicated malaria case management in the Peruvian Amazon.

BACKGROUND: Case management is one of the principal strategies for malaria control. This study aimed to estimate the economic costs of uncomplicated malaria case management and explore the influence of health-seeking behaviours on those costs. METHODS: A knowledge, attitudes and practices (KAP) survey was applied to 680 households of fifteen communities in Mazan-Loreto in March 2017, then a socio-economic survey was conducted in September 2017 among 161 individuals with confirmed uncomplicated malaria in the past 3 months. Total costs per episode were estimated from both provider (Ministry of Health, MoH) and patient perspectives. Direct costs were estimated using a standard costing estimation procedure, while the indirect costs considered the loss of incomes among patients, substitute labourers and companions due to illness in terms of the monthly minimum wage. Sensitivity analysis evaluated the uncertainty of the average cost per episode. RESULTS: The KAP survey showed that most individuals (79.3%) that had malaria went to a health facility for a diagnosis and treatment, 2.7% received those services from community health workers, and 8% went to a drugstore or were self-treated at home. The average total cost per episode in the Mazan district was US$ 161. The cost from the provider's perspective was US$ 30.85 per episode while from the patient's perspective the estimated cost was US$ 131 per episode. The average costs per Plasmodium falciparum episode (US$ 180) were higher than those per Plasmodium vivax episode (US$ 156) due to longer time lost from work by patients with P. falciparum infections (22.2 days) than by patients with P. vivax infections (17.0 days). The delayed malaria diagnosis (after 48 h of the onset of symptoms) was associated with the time lost from work due to illness (adjusted mean ratio 1.8; 95% CI 1.3, 2.6). The average cost per malaria episode was most sensitive to the uncertainty around the lost productivity cost due to malaria. CONCLUSIONS: Despite the provision of free malaria case management by MoH, there is delay in seeking care and the costs of uncomplicated malaria are mainly borne by the families. These costs are not well perceived by the society and the substantial financial impact of the disease can be frequently undervalued in public policy planning.

Anti-MSP-10 IgG indicates recent exposure to Plasmodium vivax infection in the Peruvian Amazon.

BACKGROUNDSerological tools for the accurate detection of recent malaria exposure are needed to guide and monitor malaria control efforts. IgG responses against Plasmodium vivax and P. falciparum merozoite surface protein-10 (MSP10) were measured as a potential way to identify recent malaria exposure in the Peruvian Amazon.METHODSA field-based study included 470 participants in a longitudinal cohort who completed a comprehensive evaluation: light microscopy and PCR on enrollment, at least 1 monthly follow-up by light microscopy, a second PCR, and serum and dried blood spots for serological analysis at the end of the follow-up. IgG titers against novel mammalian cell-produced recombinant PvMSP10 and PfMSP10 were determined by ELISA.RESULTSDuring the follow-up period, 205 participants were infected, including 171 with P. vivax, 26 with P. falciparum, 6 with infections by both species but at different times, and 2 with mixed infections. Exposure to P. vivax was more accurately identified when serological responses to PvMSP10 were obtained from serum (sensitivity, 58.1%; specificity, 81.8%; AUC: 0.76) than from dried blood spots (sensitivity, 35.2; specificity, 83.5%; AUC: 0.64) (PAUC < 0.001). Sensitivity was highest (serum, 82.9%; dried blood spot, 45.7%) with confirmed P. vivax infections occurring 7-30 days before sample collection; sensitivity decreased significantly in relation to time since last documented infection. PvMSP10 serological data did not show evidence of interspecies cross-reactivity. Anti-PfMSP10 responses poorly discriminated between P. falciparum-exposed and nonexposed individuals (AUC = 0.59; P > 0.05).CONCLUSIONAnti-PvMSP10 IgG indicates recent exposure to P. vivax at the population level in the Amazon region. Serum, not dried blood spots, should be used for such serological tests.FUNDINGCooperative agreement U19AI089681 from the United States Public Health Service, NIH/National Institute of Allergy and Infectious Diseases, as the Amazonian International Center of Excellence in Malaria Research.