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Background Plasmodium falciparum pigment-containing leucocytes (PCLs) are associated with adverse clinical manifestations of severe malaria in African children. However, limited data exist on the association of PCLs in settings outside of Africa. Methods Thin films on peripheral blood slides obtained from children ages 6 months–10 y with severe malaria were examined for PCLs. The intraleucocytic pigment data were correlated with clinical phenotypic data such as severe anaemia, metabolic acidosis and coma to determine the association of PCLs with clinical phenotypes of severe malaria and outcome. Results Of the 169 children with severe P. falciparum malaria confirmed by microscopy, 76% (129/169) had PCLs. Compared with children without PCLs, the presence (adjusted odds ratio [AOR] 3.2 [95% confidence interval {CI} 1.5 to 6.9], p≤0.01) and quantity (AOR 1.0 [95% CI 1.0 to 1.1], p=0.04) of pigment-containing monocytes (PCMs) was significantly associated with severe anaemia, while the quantity of both PCMs (AOR 1.0 [95% CI 1.0 to 1.1], p≤0.01) and pigment-containing neutrophils (AOR 1.0 [95% CI 1.0 to 1.1], p=0.01) was significantly associated with metabolic acidosis. Plasma P. falciparum histidine-rich protein-2 level negatively correlated with the platelet count (r=−0.5, p≤0.01) in patients with PCLs and no PCLs. Conclusions In Papua New Guinean children with severe P. falciparum malaria, the presence and quantity of PCLs are predictors of disease severity, severe anaemia and metabolic acidosis. [ABSTRACT FROM AUTHOR]

Objectives: Malaria is one of the most important parasitic infectious diseases worldwide. Despite the scale-up of effective antimalarials, mortality rates from severe malaria (SM) remain significantly high; thus, numerous trials are investigating both antimalarials and adjunctive therapy. This review aimed to summarise all the outcome measures used in trials in the last 10 years to see the need for a core outcome set.Methods: A systematic review was undertaken to summarise outcomes of individually randomised trials assessing treatments for SM in adults and children. We searched key databases and trial registries between 1 January 2010 and 30 July 2020. Non-randomised trials were excluded to allow comparison of similar trials. Trial characteristics including phase, region, population, interventions, were summarised. All primary and secondary outcomes were extracted and categorised using a taxonomy table.Results: Twenty-seven of 282 screened trials met our inclusion criteria, including 10,342 patients from 19 countries: 19 (70%) trials from Africa and 8 (30%) from Asia. A large amount of heterogeneity was observed in the selection of outcomes and instruments, with 101 different outcomes measures recorded, 78/101 reported only in a single trial. Parasitological outcomes (17 studies), neurological status (14 studies), death (14 studies) and temperature (10 studies), were the most reported outcomes. Where an outcome was reported in >1 study it was often measured differently: temperature (4 different measures), renal function (7 measures), nervous system (13 measures) and parasitology (10 measures).Conclusion: Outcomes used in SM trials are inconsistent and heterogeneous. Absence of consensus for outcome measures used impedes research synthesis and comparability of different interventions. This systematic review demonstrates the need to develop a standardised collection of core outcomes for clinical trials of treatments for SM and next steps to include the development of a panel of experts in the field, a Delphi process, and a consensus meeting. [ABSTRACT FROM AUTHOR]

Background: Severe metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings. Methods: A retrospective analysis of the 'Artesunate versus quinine in the treatment of severe falciparum malaria in African children' (AQUAMAT) trial was conducted to identify clinical features of severe metabolic acidosis and uraemia in 5425 children from nine African countries. Separate models were fitted for uraemia and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis and uraemia. Both analyses adjusted for the trial arm. A forward selection approach was used for model building of the logistic models and a threshold of 5% statistical significance was used for inclusion of variables into the final logistic model. Model performance was assessed through calibration, discrimination, and internal validation with bootstrapping. Results: There were 2296 children identified with severe metabolic acidosis and 1110 with uraemia. Prognostic features of severe metabolic acidosis among them were deep breathing (OR: 3.94, CI 2.51–6.2), hypoglycaemia (OR: 5.16, CI 2.74–9.75), coma (OR: 1.72 CI 1.17–2.51), respiratory distress (OR: 1.46, CI 1.02–2.1) and prostration (OR: 1.88 CI 1.35–2.59). Features associated with uraemia were coma (3.18, CI 2.36–4.27), Prostration (OR: 1.78 CI 1.37–2.30), decompensated shock (OR: 1.89, CI 1.31–2.74), black water fever (CI 1.58. CI 1.09–2.27), jaundice (OR: 3.46 CI 2.21–5.43), severe anaemia (OR: 1.77, CI 1.36–2.29) and hypoglycaemia (OR: 2.77, CI 2.22–3.46) Conclusion: Clinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and uraemia were independently associated with these outcomes. The model can be useful for identifying patients at high risk of these complications where laboratory assessments are not routinely available. [ABSTRACT FROM AUTHOR]

Imported malaria is often misdiagnosed due to the aspecific symptoms and lack of familiarity among clinicians. This study aims to evaluate a decade-long trend of imported malaria cases in a Belgian teaching hospital by analyzing demographics, clinical characteristics, and outcomes. Medical records of 223 patients with confirmed malaria diagnoses between 2010 and 2019 were analyzed. Most patients were male (63.2%), aged 18-65 years (77.1%), and visiting friends or relatives (40.8%). Central Africa was the most common travel destination (54.3%), and 63.7% did not take prophylaxis. Symptoms were flu-like, with fever (91.9%) being most prevalent. P. falciparum was identified in 88.3% of cases. A high proportion of severe cases (41.7%) and a low mortality rate (0.9%) were recorded. A severe form of the disease is associated with a more extended hospital stay than uncomplicated form (median of 5 vs. 4 days, p < 0.001). Thirty-five-point five percent [33/93] of patients with severe malaria have had a previous malaria infection compared to 50.8% [66/130] of uncomplicated patients (p = 0.013) wich was statistically significant. Malaria disproportionately affects VFRs traveling to Central Africa, and flu-like symptoms should raise suspicion. Prophylaxis is essential to prevent the disease, and early diagnosis is critical for effective management. A severe form of the disease is associated with a more extended hospital stay than uncomplicated form and people with a previous history of malaria have a less severe disease [ABSTRACT FROM AUTHOR]

Purpose: When considering malaria disease severity, estimation of parasitemia in erythrocytes is important, but sometimes misleading, since the infected erythrocytes may be sequestered in peripheral capillaries. In African children and Asian adults with falciparum malaria, parasitemia as assessed by quantitative PCR (qPCR) in plasma seems to be a valuable indicator of disease severity, but data on African adults as well as the impact of co-infection with HIV is lacking. Methods: In 131 patients with falciparum malaria in a public tertiary teaching hospital in Mozambique, plasma malaria parasitemia as assessed by qPCR, compared to qualitative malaria PCR in blood cell fraction, was related to malaria disease severity and HIV co-infection. Results: Of the 131 patients with falciparum malaria, based on positive qualitative PCR in the blood cell fraction, 93 patients (72%) had positive malaria qPCR in plasma. Patients with severe malaria as defined by the WHO criteria had higher malaria quantitative plasma parasitemia (median 143 genomes/µL) compared to those with uncomplicated malaria (median 55 genomes/µL, p = 0.037) in univariate analysis, but this difference was attenuated after adjusting for age, sex and HIV co-infection (p = 0.055). A quarter of the patients with severe malaria had negative qPCR in plasma. Conclusions: This study of adult African in-patients with falciparum malaria with and without HIV co-infection, neither confirms nor rejects previous studies of malaria qPCR in plasma as an indicator of disease severity in patients with falciparum malaria. There is a need for further and larger studies to clarify if parasitemia as assessed malaria qPCR in plasma could be a surrogate marker of disease severity in falciparum malaria. [ABSTRACT FROM AUTHOR]

This article presents a severe cerebral malaria patient in shock with a close contact of COVID-19 that was successfully cured in a negative pressure ward during the global pandemic of COVID-19. The patient experienced a sudden onset of high fever and coma in a designated isolation hotel after returning from Africa, and was transferred to a designated hospital. Following antimalarial therapy, blood pressure elevation, increase of blood volume, bedside hemodialysis, mechanical ventilation, plasma and platelet transfusions, the case gradual recovered.

Introduction: Malaria is still a major public health concern in the Democratic Republic of Congo. Its morbidity and mortality challenge the actual strategies of the fight agains malaria. This study was aimed to describe the epidemiology, the clinical caracteristics and the risk factors of death associated to severe malaria in the pediatric population under 5 years at Sendwe Hospital of Lubumbashi. Methods: This analytical retrospective study was conducted in Lubumbashi, in the province of Haut-Katanga. All patients under 5 years hospitalized for severe malaria were registered from January 2014 to December 2016. Results: Among the 3,092 patients hospitalised during our study period, 452 (14.6%) were admitted for severe malaria. The average age was 27.04 months, the male sex was the most affected (53.54% with the sex-ratio 1.15). The most frequent forms of gravity noticed were cerebral malaria (48.23%) and severe anemia (46.90%). Death was noted in the evolution in 28.32%. Repeated convulsion (OR = 2.27; 95% CI: 1.47-3.48), coma (OR = 3.55; 95% CI: 2.19-5.74) and severe acute malnutrition (OR = 3.32; 95% CI: 1.56-7.06) were asscociated with a high risk of death. Conclusion: This research shows that severe malaria is still an important cause of morbidity and mortality among young children in Lubumbashi. Neurologic and anemic forms are the most frequent. The predictive signs of death are: repeated convulsions, coma and severe acute malnutrition. [ABSTRACT FROM AUTHOR]

Background: The criteria for defining severe malaria have evolved over the last 20 years. We aimed to assess the strength of association of death with features currently characterizing severe malaria through a systematic review and meta-analysis.Method: Electronic databases (Medline, Embase, Cochrane Database of Systematic Reviews, Thomson Reuters Web of Knowledge) were searched to identify publications including African children with severe malaria. PRISMA guidelines were followed. Selection was based on design (epidemiological, clinical and treatment studies), setting (Africa), participants (children < 15 years old with severe malaria), outcome (survival/death rate), and prognostic indicators (clinical and laboratory features). Quality assessment was performed following the criteria of the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Odds ratios (ORs) were calculated for each study and prognostic indicator, and, when a test was assessed in at least two studies, pooled estimates of ORs were computed using fixed- or random-effects meta-analysis.Results: A total of 601 articles were identified and screened and 30 publications were retained. Features with the highest pooled ORs were renal failure (5.96, 95% CI 2.93-12.11), coma score (4.83, 95% CI 3.11-7.5), hypoglycemia (4.59, 95% CI 2.68-7.89), shock (4.31, 95% CI 2.15-8.64), and deep breathing (3.8, 95% CI 3.29-4.39). Only half of the criteria had an OR > 2. Features with the lowest pooled ORs were impaired consciousness (0.58, 95% CI 0.25-1.37), severe anemia (0.76, 95% CI 0.5- 1.13), and prostration (1.12, 95% CI 0.45-2.82).Conclusion: The findings of this meta-analysis show that the strength of association between the criteria defining severe malaria and death is quite variable for each clinical and/or laboratory feature (OR ranging from 0.58 to 5.96). This ranking allowed the identification of features weakly associated with death, such as impaired consciousness and prostration, which could assist to improve case definition, and thus optimize antimalarial treatment. [ABSTRACT FROM AUTHOR]

Microvascular function and oxygen consumption affect oxygen homeostasis but have not been assessed in African children with malaria. Microvascular function in Tanzanian children with severe malaria (SM) or uncomplicated malaria were 39% and 72%, respectively, of controls (P < .001). Uncomplicated malaria (P = .04), not SM (P = .06), children had increased oxygen consumption compared with controls. [ABSTRACT FROM AUTHOR]

The molecular arms race between humans and Plasmodium falciparum in Africa resulted in selection of sickle-cell disease, which, on balance, protects heterozygote carriers against severe malaria. Band et al. discovered that parasites counter-adapt and can overcome disease resistance by identifying parasite genome signatures, termed P. falciparum sickle-associated (Pfsa) variants. [ABSTRACT FROM AUTHOR]

Over 90% of deaths attributable to malaria are in African children under 5 years old. Yet, new treatments are often tested primarily in adult patients and extrapolations have proven to be sometimes invalid, especially in dosing regimens. For studies in severe malaria an additional complication is that the decline in severe malaria in adult patients precludes sufficiently powered trials in adults, before the intervention can be tested in the ultimate target group, paediatric severe malaria. In this paper we propose an alternative pathway to the development of drugs for use in paediatric severe malaria. We argue that following the classical phase I and II studies, small safety and efficacy studies using well-chosen surrogate endpoints in adult severe malaria be conducted, instead of larger mortality endpoint trials. If the drug appears safe and promising small pilot studies in paediatric severe malaria using the same endpoints can follow. Finally, with carefully observed safeguards in place to ensure high ethical standards, promising candidate interventions can be taken forward into mortality endpoint, well-powered, large paediatric studies in African children with severe malaria. Given the available research capacity, limited numbers of prudently selected interventions can be studied in phase III trials, and adaptive designs should be considered. [ABSTRACT FROM AUTHOR]

Background: Extensive studies investigating the role of host genetic factors during malaria associate glucose-6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency had been reported to associate with anti-malarial drug induced with haemolytic anaemia. Methods: A total of 301 Gabonese, Ghanaian, and Kenyan children aged 6–120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A+) and deficient (type A−) genotypes were determined by direct sequencing of the common African mutations G202A and A376G. Furthermore, multivariate analyses were executed to associate possible contributions of G6PD deficiency with baseline haemoglobin levels, parasitaemia and with severe malarial anaemia. Results: Two hundred and seventy-eight children (132 females and 146 males) were successfully genotyped for G6PD variants. The overall prevalence of G6PD deficiency was 13 % [36/278; 3 % (4/132) female homozygous and 22 % (32/146) male hemizygous], 14 % (40/278) children were female heterozygous while 73 % (202/278) were G6PD normal [67 % (88/132) females and 78 % (114/146) males] individuals. Multivariate regression revealed a significant association of moderately and severely deficient G6PD genotypes with haemoglobin levels according to the baseline data (p < 0.0001; G6PD heterozygous: p < 0.0001; G6PD deficient: p = 0.009), but not with severe malarial anaemia (p = 0.66). No association of G6PD genotypes with baseline parasitaemia. Conclusions: In this study, moderately (type A+) and severely (type A−) G6PD deficiency showed significant association with lower haemoglobin concentrations at baseline in African children with severe malaria without leading to severe malarial anaemia. In addition, there was no association of G6PD variant types with parasite densities on admission. [ABSTRACT FROM AUTHOR]

Background. Parenteral artesunate is recommended as first-line therapy for severe malaria. While its efficacy is firmly established, data on safety are still incomplete. Delayed hemolysis has been described in hyperparasitemic nonimmune travelers, but it is unknown if African children are equally at risk.Methods. Children aged 6 to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambaréné, Gabon, and Kumasi, Ghana. The primary outcome was incidence of delayed hemolysis on day 14.Results. In total, 72 children contributed complete data sets necessary for primary outcome assessment. Delayed hemolysis was detected in 5 children (7%), with 1 child reaching a nadir in hemoglobin of 2.8 g/dL. Patients with delayed hemolysis had higher parasite counts on admission (geometric mean parasite densities (GMPD) 306 968/µL vs 92 642/µL, P = .028) and were younger (median age: 24 months vs 43 months, P = .046) than the rest of the cohort. No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed.Conclusions. Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria. Physicians should be aware of this complication and consider prolonged follow-up.Clinical Trials Registration. Pan-African Clinical Trials Registry: PACTR201102000277177 (www.pactr.org). [ABSTRACT FROM AUTHOR]

Sequestration of Plasmodium falciparum-infected erythrocytes ( Pf IE) in the capillaries of the central nervous system ( CNS) is the pathognomonic feature of cerebral malaria, a condition frequently leading to death. Sequestration of Pf IE in the placental intervillous spaces is the characteristic feature of malaria in pregnancy and is associated with low birthweight and prematurity. Although both patterns of sequestration are thought to result from the expression of different parasite proteins involved in cytoadhesion to human receptors, scant information exists on whether both conditions can coexist and whether this can lead to death. We conducted a prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary-level referral hospital in Maputo, Mozambique, between October 2002 and December 2006. Extensive sampling of all major viscera was performed. All cases showing parasites in any of the viscera were included in the analysis. From 317 complete autopsies Pf IEs were identified in ten women (3.2%). All cases showed massive accumulation of Pf IE in small capillaries of the CNS but also in most visceral capillaries (heart, lung, kidney, uterus). Placental tissue, available in four cases, showed a massive accumulation of maternal Pf IE in the intervillous space. Coma (six women) and dyspnoea (five women) were the most frequent presenting clinical symptoms. In conclusion, massive visceral sequestration of Pf IE with significant involvement of the CNS is an infrequent but definite direct cause of maternal death in endemic areas of Africa. The Pf IE sequestered in cerebral capillaries and the placenta coexist in these fatal cases. [ABSTRACT FROM AUTHOR]

Abstract: The capacity of Plasmodium falciparum-infected red blood cells to bind uninfected red blood cells (“rosetting”) has been associated with high parasite density in numerous geographic areas and with severe malaria in African children. We summarize here the associations that have emerged from field studies and describe the various experimental models of rosetting that have been developed. A variety of erythrocyte receptors, several serum factors and a number of rosette-mediating PfEMP1 adhesins have been identified. Several var genes code for rosette-forming PfEMP1 adhesins in each P. falciparum genome, so that each clonal line has the capacity to generate distinct types of rosettes. To clarify their respective role in malaria pathogenesis, each of the multiple ligand/receptor interactions should be further studied for fine specificity, binding affinity and the impact of the large population polymorphism of the parasite variant repertoires should be assessed. Interestingly, some major human erythrocyte surface polymorphisms have been identified as affecting rosette formation, consistent with a role for rosetting in life-threatening falciparum malaria. [Copyright &y& Elsevier]

Summary: The Severe Malaria in African Children (SMAC) network was established to conduct mortality-based trials. Although falciparum malaria kills more than one million children each year, single centers cannot enroll enough patients to detect reductions of 20–30% in mortality rates. Our aim was to quantify and describe severe malaria across a variety of epidemiological settings so that we could design intervention studies with more precise sample size estimates. We used a standardized surveillance mechanism to capture clinical, laboratory and outcome data on all parasitemic children admitted to hospital. Between December 2000 and December 2003, 20333 patients were enrolled at five sites. The frequency of severe malaria syndromes (cerebral malaria, severe malarial anemia and acidosis) differed between sites, as did the syndrome-specific mortality rates. Intervention studies targeted at reducing mortality in one or a combination of severe malaria syndromes would require 3–4 years to complete within the existing network. These data provide more accurate estimates of the disease burden of children hospitalized for malaria in sub-Saharan Africa. Networks are required to recruit enough patients for mortality-based studies and to encompass the epidemiological diversity of malaria in sub-Saharan Africa. SMAC represents the first effort to develop this capacity. [Copyright &y& Elsevier]

Objectives Age and transmission intensity are known to influence the manifestations of severe falciparum malaria in African children. However, it is unclear how specific clinical features such as seizures, impairment of consciousness, or respiratory distress vary with the parasite load and transmission intensity. We examined how the peripheral parasite load varies with transmission intensity and how this influences the symptoms and manifestations of severe malaria in children under 5 years in three areas with different malaria transmission intensity across Uganda. Methods We consecutively recruited 617 children with severe malaria presenting to three hospitals in areas with very low (51), moderate (367) and very high (199) transmission intensities and compared the age, admission parasite density and proportions of patients with different manifestations of severe disease. Results The median age (months) was inversely proportional to transmission intensity and declined with rising transmission (26.4 in very low, 18.0 in moderate and 9.0 under very high transmission). The highest proportion of patients reporting previous malaria admissions came from the area with moderate transmission. The geometric mean parasite density (18 357, 32 508 and 95 433/ μl) and the proportion of patients with seizures (13.7%, 36.8% and 45.7%, P < 0.001) from very low, moderate and very high transmission respectively, increased with rising transmission. A linear increase with transmission was also observed in the proportion of those with repeated seizures (9.8%, 13.4% and 30.2%, P < 0.001) or impaired consciousness (7.8%, 12.8% and 18.1%, P = 0.029) but not respiratory distress. The proportion of patients with severe anaemia (19.6%, 24.8% and 37.7%, P = 0.002) mirrored that of patients with seizures. Conclusions These findings suggest that heavy Plasmodium falciparum parasitaemia may be important in development of seizures, severe malarial anaemia and impaired consciousness in children under 5 years of age but may not be important in the development of respiratory distress. [ABSTRACT FROM AUTHOR]

Objectives: Study of the hemodynamic profile and oxygenation variables in severe malaria to determine whether they are identical to those observed in severe bacterial infections. Design and setting: Prospective study in an intensive care unit of a West African hospital. Patients and participants: Two groups of adult patients hospitalized for severe malaria according to WHO criteria, a control group (n=13) with systemic vascular resistance of 800 dyne s–1 cm–5 or higher and a hyperkinetic group (n=16) with a level lower than 800 dyne s–1 cm–5. Twenty-nine patients participated in this study (19 semi-immune, 10 nonimmune). Interventions: Before hemodynamic study a loading dose of quinine formiate was administered: 20 mg/kg intravenously for 4 h. Artificial ventilation was used in the case of persistent hypoxemia. Measurements and results: The hemodynamic study with Swan-Ganz catheter was performed after filling with 1000 ml lactated Ringer's solution. From a clinical and a biological standpoint there was no difference between the two groups except for creatine phosphokinase, which was significantly higher in the hyperkinetic group: 2404±3654 vs. 1898±1828 IU/l. Hemodynamic and oxygenation variables showed a significant difference in cardiac index (6.1±1.2 vs. 3.9±1.2 l min–1 m–2), systemic vascular resistance (536±143 vs. 1098±170 dyne s–1 cm–5), oxygen delivery (645±163 vs. 482±186 ml min–1 m–2), and oxygen extraction (23±9% vs. 34±14%). Oxygen extraction was negatively correlated with oxygen delivery in the control group but not in the hyperkinetic group. Eight of 10 nonimmune patients (80%) were in the hyperkinetic group versus 8 of 19 semi-immune patients (42%; p<0.05). Nine patients in the hyperkinetic group (69%) and seven of the control group (46%) died (NS). Conclusions: In contrast to severe bacterial infections, severe malaria does not always induce hyperkinetic-type hemodynamic changes. Such changes are observed mostly in nonimmune subjects. [ABSTRACT FROM AUTHOR]

Most deaths from severe falciparum malaria occur within 24 h of presentation to a hospital. Intravenous (i.v.) artesunate is the first-line treatment for severe falciparum malaria, but its efficacy may be compromised by delayed parasitological responses. In patients with severe malaria, the life-saving benefit of the artemisinin derivatives is their ability to clear circulating parasites rapidly, before they can sequester and obstruct the microcirculation. To evaluate the dosing of i.v. artesunate for the treatment of artemisinin-sensitive and reduced ring stage sensitivity to artemisinin severe falciparum malaria infections, Bayesian pharmacokinetic-pharmacodynamic modeling of data from 94 patients with severe malaria (80 children from Africa and 14 adults from Southeast Asia) was performed. Assuming that delayed parasite clearance reflects a loss of ring stage sensitivity to artemisinin derivatives, the median (95% credible interval) percentage of patients clearing ≥99% of parasites within 24 h (PC24≥99%) for standard (2.4 mg/kg body weight i.v. artesunate at 0 and 12 h) and simplified (4 mg/kg i.v. artesunate at 0 h) regimens was 65% (52.5% to 74.5%) versus 44% (25% to 61.5%) for adults, 62% (51.5% to 74.5%) versus 39% (20.5% to 58.5%) for larger children (≥20 kg), and 60% (48.5% to 70%) versus 36% (20% to 53.5%) for smaller children (<20 kg). The upper limit of the credible intervals for all regimens was below a PC24≥99% of 80%, a threshold achieved on average in clinical studies of severe falciparum malaria infections. In severe falciparum malaria caused by parasites with reduced ring stage susceptibility to artemisinin, parasite clearance is predicted to be slower with both the currently recommended and proposed simplified i.v. artesunate dosing regimens., (Copyright © 2021 American Society for Microbiology.)

Background: Approximately 6% of children hospitalized with severe falciparum malaria in Africa are also bacteremic. It is therefore recommended that all children with severe malaria should receive broad-spectrum antibiotics in addition to parenteral artesunate. Empirical antibiotics are not recommended currently for adults with severe malaria., Methods: Blood cultures were performed on sequential prospectively studied adult patients with strictly defined severe falciparum malaria admitted to a single referral center in Vietnam between 1991 and 2003., Results: In 845 Vietnamese adults with severe falciparum malaria admission blood cultures were positive in 9 (1.07%: 95% confidence interval [CI], .37-1.76%); Staphylococcus aureus in 2, Streptococcus pyogenes in 1, Salmonella Typhi in 3, Non-typhoid Salmonella in 1, Klebsiella pneumoniae in 1, and Haemophilus influenzae type b in 1. Bacteremic patients presented usually with a combination of jaundice, acute renal failure, and high malaria parasitemia. Four bacteremic patients died compared with 108 (12.9%) of 836 nonbacteremic severe malaria patients (risk ratio, 3.44; 95% CI, 1.62-7.29). In patients with >20% parasitemia the prevalence of concomitant bacteremia was 5.2% (4/76; 95% CI, .2-10.3%) compared with 0.65% (5/769; 0.08-1.2%) in patients with <20% parasitemia, a risk ratio of 8.1 (2.2-29.5)., Conclusions: In contrast to children, the prevalence of concomitant bacteremia in adults with severe malaria is low. Administration of empirical antibiotics, in addition to artesunate, is warranted in the small subgroup of patients with very high parasitemias, emphasizing the importance of quantitative blood smear microscopy assessment, but it is not indicated in most adults with severe falciparum malaria., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Many parts of Africa have witnessed reductions in Plasmodium falciparum transmission over the last 15 years. Since immunity to malaria is acquired more rapidly at higher transmission, the slower acquisition of immunity at lower transmission may partially offset the benefits of reductions in transmission. We examined the clinical spectrum of disease and predictors of mortality after sustained changes in transmission intensity, using data collected from 1989 to 2016.Methods: We conducted a temporal observational analysis of 18,000 children, aged 14 days to 14 years old, who were admitted to Kilifi County Hospital, Kenya, from 1989 to 2016 with malaria. We describe the trends over time of the clinical and laboratory criteria for severe malaria and associated risk of mortality.Results: During the time periods 1989-2003, 2004-2008, and 2009-2016, Kilifi County Hospital admitted averages of 657, 310, and 174 cases of severe malaria per year including averages of 48, 14, and 12 malaria-associated deaths per year, respectively. The median ages in years of children admitted with cerebral malaria, severe anaemia, and malaria-associated mortality were 3.0 (95% confidence interval (CI) 2.2-3.9), 1.1 (95% CI 0.9-1.4), and 1.1 (95% CI 0.3-2.2) in the year 1989, rising to 4.9 (95% CI 3.9-5.9), 3.8 (95% CI 2.5-7.1), and 5 (95% CI 3.3-6.3) in the year 2016. The ratio of children with cerebral malaria to severe anaemia rose from 1:2 before 2004 to 3:2 after 2009. Hyperparasitaemia was a risk factor for death after 2009 but not in earlier time periods.Conclusion: Despite the evidence of slower acquisition of immunity, continued reductions in the numbers of cases of severe malaria resulted in lower overall mortality. Our temporal data are limited to a single site, albeit potentially applicable to a secular trend present in many parts of Africa. [ABSTRACT FROM AUTHOR]

We aimed to determine risk factors for developing severe illness in patients infected with imported Plasmodium falciparum, and identify factors that can be implemented in preventive public health actions. Data of patients in Anhui province were collected from the China Information System for Disease Control and Prevention and Information System for Parasitic Disease Control and Prevention from 2012 to 2018. Epidemiological characteristics, clinical severity, and preventive measures were analyzed using descriptive statistics. Risk factors for severe malaria were identified by logistic regression. During the study period, 8.01% (53/662) of patients infected with P. falciparum developed severe malaria; the annual severe incidence rate varied from 5.93% to 10.77% and the fatality rate was 0.6%. Two models were built to analyze the delay from symptom onset to treatment; one analyzed data by stage, whereas the other analyzed data combined from all stages. In model 1, multivariate analysis identified misdiagnosis at first medical visit and patient delay as risk factors for severe malaria (odds ratio: 3.108 and 3.385, respectively, all p < 0.01). In model 2, overall delay was a significant factor of severe malaria onset (odds ratio: 4.719, p = 0.000). In both models, patients with a history of previous infection had a significantly reduced risk of developing severe malaria; high parasitemia (≥2.5%) was associated with an increased risk of severe infection. Delay between symptom onset and treatment was an important cause for development of severe disease in Anhui province. Measures to reduce delays should be used and implemented in preventive public health actions., (Copyright © 2019 Elsevier B.V. All rights reserved.)