Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin.

BACKGROUND: Information on cardiopulmonary complications in clinical malaria is sparse and diagnosis may be difficult in resource-limited areas due to lack of proper diagnostic tools and access to medical care. A case of pericardial effusion and pulmonary alterations assessed by ultrasound in a patient with uncomplicated mixed malaria infection is described. CASE PRESENTATION: A previously healthy 23-year-old male from the Amazon Basin was diagnosed with mixed infection of Plasmodium vivax and Plasmodium falciparum by peripheral blood smear. The patient presented with mild malaria symptoms without signs of severe malaria, but reported moderate chest pain and shortness of breath. Laboratory analyses revealed thrombocytopenia and anemia. The electrocardiogram had PR depressions and bedside ultrasound of the cardiopulmonary system showed pericardial effusion (18 mm) accompanied by multiple B-lines in the lungs, identified as vertical artifacts extending from the pleural line. Cardiac biomarkers were normal. The patient was treated according to national guidelines for malaria and suspected pericarditis, respectively. At follow-up on day 5, the pericardial effusion (9mm) and B-lines had markedly decreased. By day 21 the patient was asymptomatic, had completed the treatment, and the electrocardiogram and ultrasound findings had normalized. CONCLUSIONS: This case report highlight the usefulness of bedside ultrasound to identify cardiopulmonary involvement in patients with uncomplicated malaria and relevant symptoms.

Prevalence of rheumatic heart disease in adults from the Brazilian Amazon Basin.

BACKGROUND: Rheumatic heart disease (RHD) continues to be a burden in low- and middle-income countries and prevalence estimates are lacking from South America. We aimed to determine the prevalence of RHD in the Brazilian Amazon Basin. METHODS: We examined a random sample of adults (≥18 years) from the general population, who underwent echocardiographic image acquisition by a medical doctor. All images were analyzed according to (i) the 2012 World Heart Federation criteria and (ii) a simplified algorithm for RHD from a previously validated risk score (categories: low-, medium-, high-risk) which involved assessment of the mitral valve (leaflet thickening and excessive motion, regurgitation jet length) and aortic valve (thickening and any regurgitation). RESULTS: A total of 488 adults were screened (mean age 40 ± 15 years, 38% men). The prevalence of RHD was 39/1000 adults (n = 17 definite and n = 2 borderline). Fourteen (74%) had pathological mitral regurgitation, four (21%) mitral stenosis, 0 (0%) pathological aortic regurgitation and six (32%) both mitral and aortic valve disease. None had a prior diagnosis of RHD, 10 (53%) had positive cardiac auscultation and two (11%) reported a history of rheumatic fever. The simplified algorithm identified four (21%) adults as low-risk, six (32%) as intermediate, and nine (47%) as high-risk. CONCLUSIONS: The prevalence of RHD was 39/1000 in adults from the Brazilian Amazon Basin, indicating the need for screening programs in remote areas. A simplified model was only able to categorize every second case of RHD as high-risk. External validation of simplified screening models to increase feasibility in clinical practice are encouraged.

Potential role of transthoracic echocardiography for screening LV systolic dysfunction in patients with a history of dengue infection. A cross-sectional and cohort study and review of the literature.

BACKGROUND: Dengue virus can affect the cardiovascular system and men may be at higher risk of severe complications than women. We hypothesized that clinical dengue virus (DENV) infection could induce myocardial alterations of the left ventricle (LV) and that these changes could be detected by transthoracic echocardiography. METHODOLOGY/PRINCIPAL FINDINGS: We examined individuals from Acre in the Amazon Basin of Brazil in 2020 as part of the Malaria Heart Study. By questionnaires we collected information on self-reported prior dengue infection. All individuals underwent transthoracic echocardiography, analysis of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). We included 521 persons (mean age 40±15 years, 39% men, 50% urban areas) of which 253 (49%) had a history of dengue infection. In multivariable models adjusted for clinical and sociodemographic data, a history of self-reported dengue was significantly associated with lower LVEF (ß = -2.37, P < 0.01) and lower GLS (ß = 1.08, P < 0.01) in men, whereas no significant associations were found in women (P > 0.05). In line with these findings, men with a history of dengue had higher rates of LV systolic dysfunction (LVEF < 50% = 20%; GLS < 16% = 17%) than those without a history of dengue (LVEF < 50% = 7%; GLS < 16% = 8%; P < 0.01 and 0.06, respectively). CONCLUSIONS/SIGNIFICANCE: The findings of this study suggest that a clinical infection by dengue virus could induce myocardial alterations, mainly in men and in the LV, which could be detected by conventional transthoracic echocardiography. Hence, these results highlight a potential role of echocardiography for screening LV dysfunction in participants with a history of dengue infection. Further larger studies are warranted to validate the findings of this study.

Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil.

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin. We also examined the relationship between B-lines and left ventricular ejection fraction. We performed eight-zone LUS, echocardiography, and blood smears in 94 adults (mean age 40 years, 54% men) with uncomplicated malaria and 449 controls without heart failure, renal insufficiency or lung disease (mean age 41 years, 38% men). Examinations of adults with malaria were repeated after antimalarial treatment, corresponding to a median of 30 days (interquartile range [IQR] 27-39). Adults with malaria suffered from Plasmodium vivax (N = 70, median 2,823 [IQR 598-7,698] parasites/µL) or P. falciparum (N = 24, median 1,148 [IQR 480-3,128] parasites/µL). At baseline, adults with malaria more frequently had ≥ 3 B-lines (summed across eight zones) compared with controls (30% versus 2%, P value < 0.001), indicating higher lung density. When examinations were repeated, only 6% of adults with malaria had ≥ 3 B-lines at follow-up, which was significant lower compared with baseline (median reduction 3 B-line; P value < 0.001). B-lines were not significantly associated with left ventricular ejection fraction in adults with malaria. In conclusion, B-lines detected by LUS were more frequent in adults with uncomplicated malaria compared with controls and decreased after completed antimalarial treatment.

Whole genome sequencing reveals large deletions and other loss of function mutations in Mycobacterium tuberculosis drug resistance genes.

Drug resistance in Mycobacterium tuberculosis, the causative agent of tuberculosis disease, arises from genetic mutations in genes coding for drug-targets or drug-converting enzymes. SNPs linked to drug resistance have been extensively studied and form the basis of molecular diagnostics and sequencing-based resistance profiling. However, alternative forms of functional variation such as large deletions and other loss of function (LOF) mutations have received much less attention, but if incorporated into diagnostics they are likely to improve their predictive performance. Our work aimed to characterize the contribution of LOF mutations found in 42 established drug resistance genes linked to 19 anti-tuberculous drugs across 32689 sequenced clinical isolates. The analysed LOF mutations included large deletions (n=586), frameshifts (n=4764) and premature stop codons (n=826). We found LOF mutations in genes strongly linked to pyrazinamide (pncA), isoniazid (katG), capreomycin (tlyA), streptomycin (e.g. gid) and ethionamide (ethA, mshA) (P<10-5), but also in some loci linked to drugs where relatively less phenotypic data is available [e.g. cycloserine, delaminid, bedaquiline, para-aminosalicylic acid (PAS), and clofazimine]. This study reports that large deletions (median size 1115 bp) account for a significant portion of resistance variants found for PAS (+7.1% of phenotypic resistance percentage explained), pyrazinamide (+3.5%) and streptomycin (+2.6%) drugs, and can be used to improve the prediction of cryptic resistance. Overall, our work highlights the importance of including LOF mutations (e.g. large deletions) in predicting genotypic drug resistance, thereby informing tuberculosis infection control and clinical decision-making.

Prevalence of Cardiovascular Complications in Malaria: A Systematic Review and Meta-Analysis.

Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of cardiovascular complications in symptomatic malaria patients. We searched databases such as Pubmed, Embase, Cochrane, and Web of Science (January 1950-April 2020) for studies reporting on cardiovascular complications in adults and children with malaria. Cardiovascular complications were defined as abnormalities in electrocardiogram (ECG), cardiac biomarkers, and echocardiography on admission or during outpatient examination. Studies of patients with known heart disease or cardiovascular evaluation performed after the start of intravenous antimalarial medication were excluded. The study was registered in International Prospective Register of Systematic Reviews (PROSPERO) (No.: CRD42020167672). The literature search yielded 1,243 studies, and a total of 43 studies with symptomatic malaria patients were included. Clinical studies (n = 12 adults; n = 5 children) comprised 3,117 patients, of which a majority had Plasmodium falciparum (n = 15) and were diagnosed with severe malaria (n = 13). In random-effects models of adults, the pooled prevalence estimate for any cardiovascular complication was 7% (95% CI: 5-9). No meta-analysis was conducted in children, but the range of abnormal ECG was 0-8%, cardiac biomarkers 0-57%, and echocardiography 4-9%. We analyzed 33 cases (n = 10 postmortem), in which the most common cardiovascular pathologies were myocarditis and acute coronary syndrome. All histopathological studies found evidence of parasitized red blood cells in the myocardium. Cardiovascular complications are not uncommon in symptomatic adults and children with malaria. Additional studies investigating malaria and cardiovascular disease are encouraged.