Severe Falciparum Malaria Research Articles

PfEMP1-Specific Immunoglobulin G Reactivity Among Beninese Pregnant Women With Sickle Cell Trait.

BackgroundSickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria but not against placental malaria (PM). In this study, P falciparum erythrocyte membrane protein (PfEMP1)-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants.MethodsPlasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure immunoglobulin (Ig)G levels to 6 recombinant PfEMP1 proteins and 3 corresponding native proteins expressed on the infected erythrocyte (IE) surface. Immunoglobulin G-mediated inhibition of VAR2CSA+ IEs adhesion to chondroitin sulfate A (CSA) was also tested.ResultsLevels of PfEMP1-specific IgG were similar in the 2 groups, except for native IT4VAR09 on IEs, where IgG levels were significantly higher in HbAS women. Adjusted odds ratios for women with positive IgG to HB3VAR06 and PFD1235w suggest a lower risk of infection with these virulent variants among HbAS individuals. The percentage of IEs binding to CSA did not differ between HbAA and HbAS women, but it correlated positively with levels of anti-VAR2CSA and parity. Women with PM had lower levels of anti-VAR2CSA-specific IgG and lower IgG-mediated inhibition of IE adhesion to CSA.ConclusionsThe findings support similar malaria exposure in HbAA and HbAS women and a lack of HbAS-dependent protection against placental infection among pregnant women.

Significant differences in Fc\u03b3RIIa, Fc\u03b3RIIIa and Fc\u03b3RIIIb genes polymorphism and anti-malarial IgG subclass pattern are associated with severe Plasmodium falciparum malaria in Saudi children

BackgroundThe FcγRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children.MethodsA total of 600 volunteers were enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes were analysed using PCR amplification methods, and measurements of immunoglobulin were determined using enzyme-linked immunosorbent assay (ELISA) technique.ResultsThe data revealed that the FcγRIIa-R/R131 showed a statistically significant association with SM patients when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotype among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIIa-V/V176 genotype offered protection against SM. Moreover, SM patients carrying the FcγRIIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb-NA1/NA1 and FcγRIIIb-NA2/NA2 genotypes did not show significant differences between the UM and the MFC groups. However, the genotype FcγRIIIb-NA2/NA2 was statistically significantly associated with SM patients.ConclusionsThe data presented in this study suggest that the influence of the FcγRIIa-R/R131, FcγRIIIa-F/F176 and FcγRIIIb-NA2/NA2 genotypes are statistically significantly associated with SM patients. However, the FcγRIIa-H/H13 and FcγRIIIa-V/V176 genotypes have demonstrated a protective effect against SM when compared to UM patients. The impact of the FcyR (IIa, IIIa and IIIb) gene variants and anti-malaria IgG subclasses play an important role in susceptibility to malaria infection and disease outcome in Saudi children.

Imported Malaria: A <i>Plasmodium falciparum</i> Malaria Case in Turkey with Rarely Seen Blood Stages of Infection

Malaria is an important public health problem, with about 219 million cases, which account for 435 thousand deaths of children in Africa in 2017. The infection is transmitted by female anopheles mosquito, including Plasmodium species pathogen for human. In Turkey, no domestic cases have been reported; however, according to Annual Health Statistics, 214 imported cases were reported in 2017. Although P. vivax exactly was reported in previous years, imported Plasmodium falciparum (P. falciparum) cases have increased in the last few years. Herein, we report a case of a 41-year-old male patient who returned two weeks ago from a one-week African journey. A limited number of different blood stages of the parasite (mature trophozoite, young and mature schizont) have been seen in the examination of the peripheral smear; however, the gametocyte stage was not seen. In the present case, detecting mature stages beside the early forms at the peripheral smear could not eliminate the probability of P. falciparum. To confirm the diagnosis and regulate the treatment protocol, molecular methods were employed to differentiate the potential mixture of infection. In this case study, we propose how to approach an uncertain case of severe falciparum malaria or mixture of malaria infection combined with another Plasmodium species, as a result of limited number of different blood stages of the infection at the peripheral smear.

Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.

Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission, the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis are imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model, we re-analysed clinical and genetic data from 2220 Kenyan children with clinically defined severe malaria and 3940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one-third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.

Cellular Mechanism by Which Genetic Variations in Human ATP2B4 Gene Protect Against Severe Malaria

Background: Recent genome-wide association and cross-sectional studies have identified novel human genetic polymorphisms associated with alterations in severe malaria risk. Some of the strongest associations have been identified in the ATP2B4 gene. ATP2B4 codes for PMCA4b, the primary regulator of erythrocyte calcium concentration. Methods: To investigate the cellular mechanisms by which polymorphisms in ATP2B4 alter malaria pathogenesis, we performed in vitro assays that model malaria pathogenesis on red blood cells (RBCs) collected from individuals (n=96) with and without copies of ATP2B4 variant haplotype. Findings: We found reduced rates of PMCA4b expression (p<0.0001), calcium expulsion (p<0.0001) and Plasmodium falciparum growth in RBCs from homozygote carriers of the mutant haplotype (p<0.01). We were unable to detect any difference in adhesion or var-gene expression in malaria infected RBCs with and without the variant ATP2B4 haplotype. Interpretation: This data is consistent with the conclusion that polymorphisms in ATP2B4, protect against severe falciparum malaria by controlling parasite density rather than adhesion and invasion. Funding: This work was supported by the Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM) PhD fellowship. We acknowledge core funding to the MRC International Nutrition Group through MCA760-5QX00 from the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. Declaration of Interest: None to declare. Ethical Approval: The study proposal was reviewed and approved by the Scientific Coordinating Committee of the Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM) and ethical approval was granted by the Joint Gambia Government/Medical Research Council Ethics committee (SCC number 1421).

Identifying prognostic factors of severe metabolic acidosis and uraemia in African children with severe falciparum malaria: a secondary analysis of a randomized trial

BackgroundSevere metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings.MethodsA 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.ResultsThere 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)ConclusionClinical 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.

Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes.

Sickle-trait hemoglobin protects against severe Plasmodium falciparum malaria. Severe malaria is governed in part by the expression of the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that are encoded by var genes, specifically those variants that bind Endothelial Protein C Receptor (EPCR). In this study, we investigate the effect of sickle-trait on parasite var gene expression and function in vitro and in field-collected parasites. We mapped var gene reads generated from RNA sequencing in parasite cultures in normal and sickle-cell trait blood throughout the asexual lifecycle. We investigated sickle-trait effect on PfEMP1 interactions with host receptors CD36 and EPCR using static adhesion assays and flow cytometry. Var expression in vivo was compared by assembling var domains sequenced from total RNA in parasites infecting Malian children with HbAA and HbAS. Sickle-trait did not alter the abundance or type of var gene transcripts in vitro, nor the abundance of overall transcripts or of var functional domains in vivo. In adhesion assays using recombinant host receptors, sickle-trait reduced adhesion by 73–86% to CD36 and 83% to EPCR. Similarly, sickle-trait reduced the surface expression of EPCR-binding PfEMP1. In conclusion, Sickle-cell trait does not directly affect var gene transcription but does reduce the surface expression and function of PfEMP1. This provides a direct mechanism for protection against severe malaria conferred by sickle-trait hemoglobin.Trial Registration: ClinicalTrials.gov Identifier: NCT02645604.

MAGNETIC RESONANCE IMAGING REVEALS DYSFUNCTION OF BLOOD BRAIN BARRIER IN CEREBRAL MALARIA ALONE AND WITH MULTI ORGAN DYSFUNCTION SYNDROME.

Introduction: The underlying mechanism of cerebral malaria alone or with multiple organ dysfunction (MOD) among patients with falciparum malaria is not clearly understood. Though autopsy studies showed various types of pathological changes, during life Magnetic Resonance Imaging (MRI) can identify structural and functional modication of brain during the disease process. There have been few MRI studies of brain among adult patients with cerebral malaria (CM) but none with CM and MOD. Therefore, we have conducted this study to nd out and to compare the MRI abnormalities among patients of CM and CM with MOD. Methods: This prospective study has been conducted at VSSIMSAR, Burla in which 138 consecutive patients of severe falciparum malaria were enrolled. 119 patients after exclusion were subjected to MRI within 10 hours of admission and it was repeated as per the protocol. The diagnosis of P.falciparum malaria was done by peripheral smear or Rapid diagnostic test. The diagnosis of sever malaria was done by WHO criteria. Patients of CM were grouped into Group-1 and of CM with MOD to Group-2. Results: In the study CM and CM with MOD constituted 29 (24.4%) and 90 (75.6%) patients. MRI showed increased brain volume, vasogenic oedema, and cortical thickening in all patients of severe malaria. Cytotoxic oedema also found in 37.9% of cases of CM and 75.5% of MOD (p&lt;0.001). Infarction and haemorrhage were found in less percentage of cases. Predominant posterior swelling consistent with posterior reversible encephalopathy syndrome (PRES) is found in majority of cases of CM (48.3%) compared to frontal swelling (0.0%) (p&lt;0.001). With treatment MRI ndings improved within 72 hours of treatment. Patients who died did not show any improvement in MRI nding. Conclusion: Different type of MRI ndings at different areas of brain is possible in CM and CM with MOD. It is due to dysfunction of blood brain barrier (BBB) and it can be reversible with treatment. Therefore, intervention with drugs improving BBB may be benecial for survival.

Malaria in the Intensive Care Unit.

Most cases of severe malaria are caused by Plasmodium falciparum. Severe malaria is characterized by severe organ dysfunction. Both peripheral smear examination and rapid diagnostic test have a role in the diagnosis. Parenteral artesunate is clearly the drug of choice for the management of severe malaria. Parenteral artesunate should always be followed up with ACT.Most of the complications of severe malaria require supportive care only. The role of exchange transfusions in the management of severe malaria is questionable in the postartesunate era. Malaria in pregnancy can be quite severe and artesunate is now the drug of choice for all three trimesters. Vivax malaria is being increasingly recognized as a cause of severe malaria. The cause for this increased virulence is still not clear. Management of severe vivax malaria is similar to that of severe falciparum malaria.How to cite this article: Hegde A. Malaria in the Intensive Care Unit. Indian J Crit Care Med 2021;25(Suppl 2):S127–S129.

Pharmacogene Sequencing of a Gabonese Population with Severe Plasmodium falciparum Malaria Reveals Multiple Novel Variants with Putative Relevance for Antimalarial Treatment.

Malaria remains one of the deadliest diseases in Africa, particularly for children. While successful in reducing morbidity and mortality, antimalarial treatments are also a major cause of adverse drug reactions (ADRs). Host genetic variation in genes involved in drug disposition or toxicity constitutes an important determinant of ADR risk and can prime for parasite drug resistance. Importantly, however, the genetic diversity in Africa is substantial, and thus, genetic profiles in one population cannot be reliably extrapolated to other ethnogeographic groups. Gabon is considered a high-transmission country, with more than 460,000 malaria cases per year. Yet the pharmacogenetic landscape of the Gabonese population or its neighboring countries has not been analyzed. Using targeted sequencing, here, we profiled 21 pharmacogenes with importance for antimalarial treatment in 48 Gabonese pediatric patients with severe Plasmodium falciparum malaria. Overall, we identified 347 genetic variants, of which 18 were novel, and each individual was found to carry 87.3 ± 9.2 (standard deviation [SD]) variants across all analyzed genes. Importantly, 16.7% of these variants were population specific, highlighting the need for high-resolution pharmacogenomic profiling. Between one in three and one in six individuals harbored reduced-activity alleles of CYP2A6, CYP2B6, CYP2D6, and CYP2C8 with important implications for artemisinin, chloroquine, and amodiaquine therapy. Furthermore, one in three patients harbored at least one G6PD-deficient allele, suggesting a considerably increased risk of hemolytic anemia upon exposure to aminoquinolines. Combined, our results reveal the unique genetic landscape of the Gabonese population and pinpoint the genetic basis for interindividual differences in antimalarial drug responses and toxicity.

Sickle Cell Trait Modulates the Proteome and Phosphoproteome of Plasmodium falciparum-Infected Erythrocytes.

The high prevalence of sickle cell disease in some human populations likely results from the protection afforded against severe Plasmodium falciparum malaria and death by heterozygous carriage of HbS. P. falciparum remodels the erythrocyte membrane and skeleton, displaying parasite proteins at the erythrocyte surface that interact with key human proteins in the Ankyrin R and 4.1R complexes. Oxidative stress generated by HbS, as well as by parasite invasion, disrupts the kinase/phosphatase balance, potentially interfering with the molecular interactions between human and parasite proteins. HbS is known to be associated with abnormal membrane display of parasite antigens. Studying the proteome and the phosphoproteome of red cell membrane extracts from P. falciparum infected and non-infected erythrocytes, we show here that HbS heterozygous carriage, combined with infection, modulates the phosphorylation of erythrocyte membrane transporters and skeletal proteins as well as of parasite proteins. Our results highlight modifications of Ser-/Thr- and/or Tyr- phosphorylation in key human proteins, such as ankyrin, β-adducin, β-spectrin and Band 3, and key parasite proteins, such as RESA or MESA. Altered phosphorylation patterns could disturb the interactions within membrane protein complexes, affect nutrient uptake and the infected erythrocyte cytoadherence phenomenon, thus lessening the severity of malaria symptoms.

Pharmacokinetic Study of Rectal Artesunate in Children with Severe Malaria in Africa.

When severe malaria is suspected in children, the WHO recommends pretreatment with a single rectal dose of artesunate before referral to an appropriate facility. This was an individually randomized, open-label, 2-arm, crossover clinical trial in 82 Congolese children with severe falciparum malaria to characterize the pharmacokinetics of rectal artesunate. At admission, children received a single dose of rectal artesunate (10 mg/kg of body weight) followed 12 h later by intravenous artesunate (2.4 mg/kg) or the reverse order. All children also received standard doses of intravenous quinine. Artesunate and dihydroartemisinin were measured at 11 fixed intervals, following 0- and 12-h drug administrations. Clinical, laboratory, and parasitological parameters were measured. After rectal artesunate, artesunate and dihydroartemisinin showed large interindividual variability (peak concentrations of dihydroartemisinin ranged from 5.63 to 8,090 nM). The majority of patients, however, reached previously suggested in vivo IC50 and IC90 values (98.7% and 92.5%, respectively) of combined concentrations of artesunate and dihydroartemisinin between 15 and 30 min after drug administration. The median (interquartile range [IQR]) time above IC50 and IC90 was 5.68 h (2.90 to 6.08) and 2.74 h (1.52 to 3.75), respectively. The absolute rectal bioavailability (IQR) was 25.6% (11.7 to 54.5) for artesunate and 19.8% (10.3 to 35.3) for dihydroartemisinin. The initial 12-h parasite reduction ratio was comparable between rectal and intravenous artesunate: median (IQR), 84.3% (50.0 to 95.4) versus 69.2% (45.7 to 93.6), respectively (P = 0.49). Despite large interindividual variability, rectal artesunate can initiate and sustain rapid parasiticidal activity in most children with severe falciparum malaria while they are transferred to a facility where parenteral artesunate is available. (This study has been registered at ClinicalTrials.gov under identifier NCT02492178.).

STUDY OF ADRENAL INSUFFICIENCY IN SEVERE FALCIPARUM MALARIA WITH SHOCK KEY WORDS: Falciparum Malaria, Shock, Adrenal

Malaria remains a serious health problem in South East Asian Region (SEAR) with nearly 290 million people are estimated to be at high risk.India accounts for 77% of the regional total malarial cases.Most of deaths in malaria are due to severe falciparum malaria. Odisha is a unique state in the eastern region of India, which contributes 4% of the population and counting up to &gt;40% of total falciparum malaria cases of India. Malaria is one of the most important public health disease in Odisha. In spite of such an important disease, there are many areas on severe falciparum malarias where research work is scanty. One among of them is detection of relative adrenal insufficiency in severe falciparum malaria. As there is limited work about the relative adrenal insufficiency in severe falciparum malaria with shock and its relation to mortality. This study has been undertaken with the following aims and objectives, firstly detection of relative adrenal insufficiency in severe falciparum malaria with shock and secondly to establish the relation of mortality with or without adrenal insufficiency in severe falciparum malaria.The present study has established that relative adrenal insufficiency is an important cause contributing to shock and increased mortality. Thus addition of corticosteroid saves life and must be used in the relative adrenal insufficiency. However the firm diagnosis of relative adrenal insufficiency depends upon estimation of basal serum cortisol level &amp; post ACTH serum cortisol level. As corticosteroid reduces the mortality rate, it should be empirically used in critically ill severe falciparum malaria cases with shock.

Development and Validation of an In Silico Decision Tool To Guide Optimization of Intravenous Artesunate Dosing Regimens for Severe Falciparum Malaria Patients.

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.

Analysis of one case of artemether-resistant severe falciparum malaria

To analyze the clinical data of one case of artemether-resistant severe falciparum malaria in peacekeeping mission area in the Democratic Republic of the Congo in December 2019, so as to provide the reference for the treatment of falciparum malaria. The clinical history, laboratory diagnosis and treatment of one patient with artemether resistance in severe plasmodium falciparum malaria were reviewed. The patient, a Chinese engineer, had engaged in UN peace-keeping operation in the Democratic Republic of the Congo since Sep 23 2019. He was admitted to Chinese Level II Hospital on Dec 8, 2019 with the complaint of headache and weakness for 3 days, with fever and jaundice for 1 day. Plasmodium falciparum was diagnosed definitively by rapid diagnostic test (RDT) and blood film smear. Parasite density was 53 200 /μL on admission, then the parasite clearance rate was monitored by blood film smear. Artemether was intramuscularly injected once a day for two days. But the patient’s symptoms were not improved, and the parasite density was still high (36 380 /μL) on Dec 10, 2019. The possibility of resistance to artemether was considered, so artesunate was intravenously injected for anti-malarial treatment. Meanwhile the comprehensive treatment such as liver protection was continued. December 13, 2019, the patient’ s condition was improved, and the anti-malarial therapy was changed to oral compound dihydroartemisinin tablets. The parasitemia was undetectable since Dec 14, 2019. The patients were discharged on Dec 20, 2019, and followed up for 3 months without recurrence. The therapeutic efficacy for falciparum malaria has been severely threatened by artemisinin resistance, not only for malaria in peacekeeping mission area, but also for imported malaria. The timely diagnosis and treatment for falciparum malaria play a critical role, meanwhile the survey of artemisinin resistance should be emphasized. 摘要 ：收集刚果(金)维和任务区2019年12月收治的1例蒿甲醚耐药重症恶性疟病例诊疗过程中的临床和实验室 检验资料, 并进行相关分析, 为今后恶性疟疾的临床治疗提供思路。该患者为中国工兵, 自2019年9月23日参与联合 国刚果(金)维和行动。2019年12月8日患者因“头痛、乏力3 d, 发热伴皮肤及巩膜黄染1 d”就诊于中国二级医院。经 血涂片镜检为恶性疟疾, 疟原虫计数为53 200/μL。人院后予以蒿甲醚肌肉注射行抗疟治疗, 并通过血涂片监测疟原 虫清除率。2019年12月10日患者仍持续发热, 伴腹痛、呼吸急促, 血涂片疟原虫计数36 380/μL。考虑蒿甲醚耐药可 能, 改用青蒿琥酯静脉注射, 继续行保肝等综合治疗。2019年12月13日患者症状改善, 改用口服复方双氢青蒿素片治 疗。2019年12月14日患者血涂片疟原虫转阴, 并于2019年12月20日出院。随访3个月, 患者无发热等不适, 复査血 涂片阴性, 证实该疟疾病例已痊愈。青蒿素耐药性的发生, 给维和任务区及国内输人性恶性疟疾的治疗带来严重的威 胁 , 必须做到早发现、早诊断、早治疗 , 同时重视耐药性的监测。

Clinical characteristics of 66 imported malaria cases in Xixi Hospital of Hangzhou

Objective To analyze the clinical data and drug treatment of malaria patients Xixi Hospital of Hangzhou, February 2014 – December 2019, and we provide reference data for early clinical diagnosis, assessment of severity and treatment, and promote rational clinical medication. Methods A total of 66 malaria patients admitted to hospital from February 2014 to December 2019 were collected to distinguish mild and severe cases. The laboratory test results and drug use of the two groups were compared, and the indicators of the two groups were analyzed by multi-factor binary Logistic Stepwise regression analysis. Results In the treatment of 17 patients with severe falciparum malaria, 10 patients artesunate injection and subsequent dihydroartemisinin-piperaquine tablets were used to consolidate the treatment, and the treatment effect was good. Among 34 patients with mild falciparum malaria, 28 patients were treated with dihydroartemisinin-piperaquine tablets alone, with sensitive effect and high cure rate. For 8 cases of vivax malaria and 4 cases of ovale malaria, 6 patients were treated with chloroquine phosphate plus primaquine phosphate 8-day regimen, and 6 patients were treated with artemisinin-based drugs, and the treatment effect was good. There was statistically significant difference in age, cure time, white blood cells (WBC), red blood cells, hemoglobin, platelets, aspartate transaminase, total bilirubin, C-reactive protein and procalcitonin (PCT) between mild group and severe group ( P <0.05). Multi-factor binary Logistic Stepwise regression analysis showed that the related factors influencing the severity of malaria included age, WBC and PCT. Conclusion Artemisinin-based injections combined with ACTs (Combinatorial therapy) are more effective in treating severe and malignant diseases. Artemisinin alone is effective in the treatment of vivax malaria and ovale malaria in the absence of preferred drugs. There are many factors, such as age, cure time, white blood cells, red blood cells, hemoglobin, platelets, aspartate transaminase, total bilirubin, C-reactive protein and procalcitonin, influencing the severity of malaria, among which age, leukocyte and procalcitonin are of great significance for the prediction and evaluation of malaria severity. 摘要:目的 分析杭州市西溪医院2014年2 月一2019年 12月收治的疟疾患者临床资料及药物治疗情况,为临床早 期诊断、评估轻重以及治疗提供参考数据,促进临床合理用药。 方法 收集2014年 2 月一2019年12月收治人院的66 例疟疾患者资料,分为轻症组和重症组,对两组患者的实验室检测指标结果、药物使用情况进行比较,并采用多因素二 元 Logistic 对两组患者的指标作逐步回归分析。 结果 17 例重症恶性疟患者治疗中, 10 例患者尽早、足量、足疗程使用 青蒿琥酯针及后续双氢青蒿素哌喹片巩固治疗,效果良好。 34 例轻症恶性疟疾患者, 28 例单独使用双氢青蒿素哌喹 片,效果敏感,治愈率高。 8 例间日疟和 4 例卵形疟, 6 例患者使用磷酸氯喹加磷酸伯氨喹八日方案, 6 例患者选用青蒿 素类药物,效果均良好。经Pearson单因素分析,轻症组与重症组在年龄、治愈时间、白细胞、红细胞、血红蛋白、血小板、谷草转氨酶、总胆红素、C-反应蛋白及降钙素原间差异具有统计学意义( P <0.05);经多元 Logistic 回归分析,影响疟疾轻 重症分型的相关因素包括:年龄、白细胞计数、降钙素原。 结论 青蒿素类注射液治疗后联用青蒿素类复方(ACTs)能 更有效治疗重症恶性疟疾。在缺乏首选药物的情况下单用青蒿素类药物治疗间日疟、卵形疟效果良好。影响疟疾发 病后重症化的因素有年龄、治愈时间、白细胞、红细胞、血红蛋白、血小板、谷草转氨酶、总胆红素、C-反应蛋白及降钙素 原,其中年龄、白细胞及降钙素原对疟疾严重程度的预测评估意义重大。

Comparative Efficacy and Safety of the Artemisinin Derivatives Compared to Quinine for Treating Severe Malaria in Children and Adults: A Systematic Update of Literature and Network Meta-Analysis

Background: The artemisinin derivatives are the preferred antimalaria drugs for treating severe Plasmodium falciparum malaria. However, their clinical effectiveness among each other is unknown. Methods: Review protocol was registered with PROSPERO, CRD42020218190. We updated the search strategies of three Cochrane systematic reviews which included published and unpublished randomised control trials (RCTs) that have compared specific artemisinin derivatives to quinine in treating severe malaria. Search included CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and trial registries up to February 2021. We screened studies, extracted data, assessed risk of bias, and quality of evidence in duplicate. Separate analyses in the frequentist framework, using a random effects model, with quinine as reference, were conducted for adults and children, and rankings were produced using p-scores to assess mortality, parasite clearance, coma recovery, fever clearance, neurological sequela and adverse events. Findings: Searches identified 818 citations, 33 RCTs were eligible. We pooled 7795 children and 3182 adults. The networks involved artesunate, artemether, rectal artemisinin, arteether and quinine. Compared to quinine, artesunate reduced mortality in children (risk ratio (RR), 0.76; 95%CI [0.65 to 0.89], moderate quality), adults (RR, 0.55; 95%CI [0.40 to 0.75], low quality), and in cerebral malaria (RR, 0.72; 95%CI [0.55 to 0.94], moderate quality).Compared to rectal artemisinin and intramuscular arteether, the efficacy and safety of parenteral artesunate, and intramuscular artemether in treating severe malaria are not clear. Rankings showed that none of the artemisinin drugs were consistently superior in all the outcomes assessed. Indirect evidence produced were of very low ratings due to suspected publication bias and imprecision. Interpretations: Artesunate reduces mortality compared to quinine for both adults and children in Asia, and Africa including cerebral malaria. The artemisinin derivatives remain the best treatment for severe malaria but their comparative clinical effectiveness is yet to be fully explored. Funding Information: Initial part of this review was done as part of Nicholas Nyaaba's MSc from the University of Oxford which was supported by the the Ghana Education Trust Fund (GETFund). Registration Details: PROSPERO, CRD42020218190. Funding Information: Initial part of this review was done as part of Nicholas Nyaaba’s MSc from the University of Oxford which was supported by the Ghana Education Trust Fund (GETFund). Declaration of Interests: The authors have no conflicts of interest to declare.

Analysis of 11 imported severe malaria cases in Jiangsu

Objective This paper analyzed 11 cases of severe malaria in Jiangsu Province, summarized the causes of severe malaria, evaluated the effect of diagnosis and treatment, and provided scientific basis for formulating feasible treatment measures of severe malaria. Methods The case information, epidemiological investigation reports and inpatient medical records of 11 severe malaria cases in Jiangsu Province in 2019 were collected from the Infectious Disease Report Information Management System and Parasitic Disease Prevention and Control Information Management System. The onset time, clinical manifestations, diagnosis process and treatment of severe malaria cases were summarized and analyzed. Results Totally 11 cases of severe malaria, including 10 cases of falciparum malaria, and 1 case of ovale malaria, were all imported cases from abroad. The shortest time of living abroad was 22 days, and the longest was 1 070 days. Four cases had malaria while abroad. All of the 10 severe cases of falciparum malaria developed within one month after they returned to China, and three of them became ill on the day they returned home. One severe case of Plasmodium ovale began onset 134 days after returning home. The average time from onset to treatment was 2.5 days, and the average interval time from visit to diagnosis was 1.81 days. There were 3 cases of coma or shock, 3 cases of severe anemia, 4 cases of acute renal failure, and 1 case of acute respiratory distress syndrome. 1 case of Plasmodium ovale had severe anemia due to spontaneous rupture of spleen. Except one case of ovale malaria was treated with dihydroartemisinin piperaquine tablets plus primaquine tablets, the other 10 severe falciparum malaria cases were treated with artesunate injection for antimalarial treatment, and all of them were cured and discharged from hospital after receiving antimalarial treatment. 11 cases of severe cases, the shortest length of stay was 9 days, the longest was 40 days, with an average of 22.64 days; the minimum hospitalization cost was 9 270 yuan, the maximum was 177 174 yuan, with an average of 81 520.76 yuan. Conclusion It is necessary to strengthen multi department cooperation to improve patients’ awareness of timely treatment, strengthen the professional knowledge and professional training of medical staff, find and treat imported malaria cases as soon as possible, so as to prevent severe malaria caused by delayed diagnosis. 摘要:目的 对江苏省11例输入性重症疟疾病例进行分析,总结重症疟疾的成因、评价诊治效果,为制定切实可行 的重症疟疾救治措施提供科学依据。 方法 收集2019年江苏省11例重症疟疾病例传染病报告信息管理系统和寄生 虫病防治信息管理系统的个案信息、流行病学调查报告以及住院病历,对重症疟疾病例的发病时间、临床表现、诊断过 程、治疗情况进行汇总分析。 结果 11例重症疟疾病例中恶性疟10例、卵形疟1例,均为境外输入性病例,在境外生活 时间最短22 d最长1 070 d在国外期间有4例曾患过疟疾。10例恶性疟重症病例均在回国后一个月内发病,其中有 3例在回国当天就发病。1例卵形疟重症病例在回国后134 d才开始发病。11例重症疟疾病例发病至就诊平均时间为 2.5 d,就诊至确诊平均时间为1.81 d。重症表现为昏迷或休克3例、重度贫血3例、急性肾功能衰竭4例、急性呼吸窘迫 综合征1例。1例卵形疟由于出现自发性脾破裂引起重度贫血。除1例卵形疟病例给予双氢青蒿素哌喹片加服伯氨喹 片治疗外,其余10例恶性疟重症病例均采用青蒿琥酯注射抗疟治疗,接受抗疟治疗后均痊愈出院。11例重症病例,住 院天数最短9 d最长40 d平均22.64 d;住院费用最少9 270元,最多177 174元,平均81 520.76元。 结论 应加强多部 门合作,提高患者及时就诊意识;加强医务人员疟疾专业知识和业务的培训,尽早发现输入性疟疾病例并及时治疗,防 止因延误诊断造成的重症疟疾。

English

BACKGROUND Malaria is a global health burden. About 300 - 500 million people suffer from the disease every year, out of whom, about 1 million succumb.1 This study was undertaken, as there has been no such study regarding the possible effect of - thalassemia and ABO blood group in Indian population on falciparum malarial infection. METHODS This is an observational study carried on in all malarial patients admitted in the Department of General Medicine, VSS Medical College &amp; Hospital, Burla, between October 2008 - September 2010. Inclusion criteria: (i) Fever with positive asexual forms of falciparum malarial parasites [thick smear, thin smear, positive quantitative buffy coat (QBC), ICT test]. (ii) WHO criteria for severe falciparum malaria2 . “Controls”: Healthy persons of about same age, sex, ethnicity and locality. Exclusion Criteria: Blood transfusion within 3 months, cases of DM, CKD, hepatitis, SCD, tuberculosis, HIV, chronic liver disease, and COPD. RESULTS 128 cases of malaria, between 15 - 75 years, both sexes, pregnant / non-pregnant were included in the study. For control, the gene frequencies were  /  29 (45.3 %),  3.7 /  27 (42.2 %) and 3.7 / 3.7 8 (12.5 %). For cases, it was found 33 (51.56 %), 25 (39.1 %) and 6 (9.4 %) respectively. In HPLC, HbA0 values of 3.7 / 3.7 (81.83  10) were &gt;  /  (77.11  21.6) &gt;  3.7 / , (64.8 ± 32.42), HbA2 values of  /  (2.1  1.4) &gt;  3.7 /  (1.8 ± 0.8) &gt; 3.7 / 3.7 (1.43  0.27). In HbF, there were nearly same number of cases in all three variants and were negligible in HbS. Anaemia, jaundice, oliguria were the predominant causes of morbidity in alpha thalassaemic patients with severe falciparum malaria. Blood group A patients had significantly higher morbidity than blood group B, AB and O. CONCLUSIONS The percentage of anaemia, coma, convulsion and death was significantly less in homozygous alpha thalassemia cases in comparison to normal alpha thalassemia and heterozygous alpha thalassemia. Above features were also found to be significantly less in blood group O patients, and significantly high in blood group A patients, when compared to other blood groups. Prevalence of heterozygous and homozygous -thalassemia was lower in cases in comparison to controls. MCV was significantly lower in homozygous alpha thalassemia patients in comparison to other genotypes of alpha thalassemia. Anaemia, jaundice, coma, shock, oliguria, being the major co-morbidity conditions, should be detected and treated early. KEYWORDS Severe falciparum Malaria, ABO Blood Group, Homozygous &amp; Heterozygous, -Thalassemia

Clinical Features and Mortality Associated with Severe Malaria in Adults in Southern Mauritania.

Severe malaria in adults is not well-studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (p < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, such as parenteral artesunate, is required to lower the mortality rate associated with severe malaria.