Features Of Severe Malaria Research Articles

Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT)

SummaryBackgroundSickle cell anaemia (SCA) has historically been associated with high levels of childhood mortality in Africa. Although malaria has a major contribution to this mortality, to date, the clinical pathology of malaria among children with SCA has been poorly described. We aimed to explore the relationship between SCA and Plasmodium falciparum malaria in further detail by investigating the burden and severity of malaria infections among children recruited with severe anaemia to the TRACT trial of blood transfusion in Africa.MethodsThis study is a post-hoc secondary analysis of the TRACT trial data, conducted after trial completion. TRACT was an open-label, multicentre, factorial, randomised controlled trial enrolling children aged 2 months to 12 years who presented with severe anaemia (haemoglobin <6·0 g/dL) to four hospitals in Africa. This secondary analysis is restricted to Uganda, where the birth prevalence of SCA is approximately 1% and malaria transmission is high. Children were classified as normal (HbAA), heterozygous (HbAS), or homozygous (HbSS; SCA) for the rs334 A→T sickle mutation in HBB following batch-genotyping by PCR at the end of the trial. To avoid confounding from SCA-specific medical interventions, we considered children with an existing diagnosis of SCA (known SCA) separately from those diagnosed at the end of the trial (unknown SCA). The outcomes considered in this secondary analysis were measures of P falciparum parasite burden, features of severe malaria, and mortality at day 28 in malaria-positive children.FindingsBetween Sept 17, 2014, and May 15, 2017, 3944 children with severe anaemia were enrolled into the TRACT trial. 3483 children from Uganda were considered in this secondary analysis. Overall, 1038 (30%) of 3483 Ugandan children had SCA. 1815 (78%) of 2321 children without SCA (HbAA) tested positive for P falciparum malaria, whereas the prevalence was significantly lower in children with SCA (347 [33%] of 1038; p<0·0001). Concentrations of plasma P falciparum histidine-rich protein 2 (PfHRP2), a marker of the total burden of malaria parasites within an individual, were significantly lower in children with either known SCA (median 8 ng/mL; IQR 0–57) or unknown SCA (7 ng/mL; 0–50) than in HbAA children (346 ng/mL; 21–2121; p<0·0001). In contrast to HbAA children, few HbSS children presented with classic features of severe and complicated malaria, but both the frequency and severity of anaemia were higher in HbSS children. We found no evidence for increased mortality at day 28 in those with SCA compared with those without SCA overall (hazard ratios 1·07 [95% CI 0·31–3·76] for known SCA and 0·67 [0·15–2·90] for unknown SCA).InterpretationThe current study suggests that children with SCA are innately protected against classic severe malaria. However, it also shows that even low-level infections can precipitate severe anaemic crises that would likely prove fatal without rapid access to blood transfusion services.FundingUK Medical Research Council, Wellcome, and UK National Institute for Health and Care Research.

Effect of health seeking behaviour of caregivers on severe malaria outcome in under-fives seen in a tertiary health institution in Nigeria.

Recognition of the symptoms and seeking prompt treatment in a health facility is a major means of reducing morbidity and prevention of mortality from severe malaria in under-fives. To document the effect of health-seeking behaviour of caregivers and severe malaria outcome in underfives seen in a tertiary health institution in Nigeria. A descriptive cross-sectional study carried out from July 2012 - June 2013. Data were obtained using a researcher-administered questionnaire. Caregivers and children (6 - 59 months) who presented with features of severe malaria according to World Health Organization criteria. Of the 120 caregivers mean [SD] age (31.4 [7.0] years) /child pairs (24 [14.7] months), 35 (29%) caregivers had appropriate health-seeking behaviour. The commonest place visited for initial healthcare before presentation was the patent medicine vendors by 87 (73%) caregivers. Seventy-seven per cent of caregivers who did not have appropriate health-seeking behaviour were from the lower family social class (p = 0.03). Caregivers whose children presented with severe anaemia were significantly more likely to have appropriate health-seeking behaviour (p =0.00). The mortality rate of severe malaria was 15 per 1000; of which 94% were children whose caregivers did not have appropriate health-seeking behaviour. Age younger than 2 years (p = 0.02), cerebral malaria (p = 0.01) and jaundice (p = 0.03) significantly predicted mortality in the children irrespective of the caregivers' health-seeking behaviour status. Less than a third of the caregivers had appropriate health-seeking behaviour for their under-fives with severe malaria, and the majority of these were from the lower family social class. Cerebral malaria and jaundice significantly predicted mortality in children with severe malaria irrespective of caregivers' health-seeking behaviour status. The study was self-sponsored by the authors.

EARLY MANAGEMENT OF MALARIA IN THE CONTEXT OF ELIMINATION: OBSERVATIONS FROM CHITWAN MEDICAL COLLEGE, NEPAL

Background: Nepal is entering a malaria elimination phase with the target for no indigenous cases set for 2025. The elimination phase is known to be a challenge due to knowledge and skills reduction as cases become rarer.&#x0D; Methods: We audited all malaria parasitology tests in Chitwan Medical College from January 2017 to December 2018. Slide positive rate, case treatment and timings were identified from case note review.&#x0D; Results: Over the 2 years, 1455 malaria tests were performed, 12 were positive, making the positive test rate at 0.83%. Eleven of these 12 case files were found. They were reviewed to find the case details. All cases were &gt;16 years old. Four cases had P. falciparum, six cases had P. vivax,and in one case, the species was not identified. Four of the 12 cases fulfilled criteria for severe malaria. All P. falciparum cases had travelled outside Nepal in the past year. Median time from symptom onset to treatment was 170 hours. Median time from attendance to anti-malarial treatment was 9 hours. Three cases did not receive guideline antibiotics according to Nepal National Protocol.&#x0D; Conclusions: In conclusion, immediate testing with malaria RDT in all febrile patients presenting to CMC for early diagnosis and prompt treatment is recommended. In addition, we urge to inform colleagues on the features of severe malaria and the national treatment protocol including use of Primaquine for progressing to elimination target.

Early Management of Malaria in the Context of Elimination: Observations from Chitwan Medical College, Nepal

Background: Nepal is entering a malaria elimination phase with the target for no indigenous cases set for 2025. The elimination phase is known to be a challenge due to knowledge and skills reduction as cases become rarer.&#x0D; Methods: We audited all malaria parasitology tests in Chitwan Medical College from January 2017 to December 2018. Slide positive rate, case treatment and timings were identified from case note review.&#x0D; Results: Over the 2 years, 1455 malaria tests were performed, 12 were positive, making the positive test rate at 0.83%. Eleven of these 12 case files were found. They were reviewed to find the case details. All cases were &gt;16 years old. Four cases had P. falciparum, six cases had P. vivax,and in one case, the species was not identified. Four of the 12 cases fulfilled criteria for severe malaria. All P. falciparum cases had travelled outside Nepal in the past year. Median time from symptom onset to treatment was 170 hours. Median time from attendance to anti-malarial treatment was 9 hours. Three cases did not receive guide­line antibiotics according to Nepal National Protocol.&#x0D; Conclusions: In conclusion, immediate testing with malaria RDT in all febrile patients presenting to CMC for early diagnosis and prompt treat­ment is recommended. In addition, we urge to inform colleagues on the features of severe malaria and the national treatment protocol includ­ing use of Primaquine for progressing to elimination target.

Severe Plasmodium vivax malaria, HIV, tuberculosis co-infection in a Sri Lankan traveller: case management and challenges during the prevention of malaria reintroduction phase

BackgroundThe country received malaria-free certification from WHO in September 2016, becoming only the second country in the WHO South East Asia region to be declared malaria-free. Imported malaria cases continue to be reported, with 278 cases reported between 2013 and 2017. The diagnosis of a severe Plasmodium vivax patient co-infected with HIV and tuberculosis is discussed with an overview of the rapid response mounted by the Anti Malaria Campaign (AMC), Sri Lanka.Case presentationA Sri Lankan gem miner who returned from Madagascar on the 6th of April 2018 presented to a private hospital for a malaria diagnostic test on the 21st April, 2 days after the onset of fever. He came on his own for this test due to the awareness he had regarding the risk of imported malaria. As the patient was positive for P. vivax malaria, he was admitted to a government hospital for further management. The patient had features of severe malaria upon admission with a systolic BP < 80 mmHg and thrombocytopaenia (38,000 cells/mm3). Treatment with IV artesunate was initiated immediately and management was carried out rapidly and efficiently by the clinicians with guidance from the staff of the AMC headquarters, which resulted in a rapid recovery of the patient. IV artesunate was followed by a course of artemether plus lumefantrine and the blood smear was negative for malaria by the 2nd day. A 14-day course of primaquine was commenced after excluding a G6PD deficiency. Due to an accidental needle stick injury of a health care worker attending on the patient was tested for HIV and subsequently tuberculosis and was found to be positive for both infections. The patient was discharged on the 1st of May with instructions for follow up visits for malaria. Management of the HIV and tuberculosis infections was attended to by the clinicians and staff of the appropriate disease control programmes (i.e. the national STD/AIDS Control Programme in Sri Lanka and the National Programme for tuberculosis control and chest diseases).ConclusionsIt is important to consider comorbid conditions and immunosuppression when a patient with a benign form of malaria presents with severe manifestations. Measures should be strengthened to prevent importation of diseases, such as malaria and AIDS through migrant workers who return from high-risk countries.

Liver Injury in Uncomplicated Malaria is an Overlooked Phenomenon: An Observational Study.

Abstract Background Liver injury is a known feature of severe malaria, but is only incidentally investigated in uncomplicated disease. In such cases, drug-induced hepatotoxicity is often thought to be the primary cause of the observed liver injury, and this can be a major concern in antimalaria drug development. We investigated liver function test (LFT) abnormalities in patients with imported uncomplicated malaria, and in Controlled Human Malaria Infection (CHMI) studies. Methods Clinical and laboratory data from 484 imported malaria cases and 254 CHMI participants were obtained from the Rotterdam Malaria Cohort database, and the Radboud University Medical Center database (between 2001 and 2017), respectively. Routine clinical LFTs, clinical profiles, parasite densities, hematological, and inflammation parameters were assessed in 217 patients with imported falciparum malaria upon admission, and from longitudinal data of 187 CHMI participants. Findings Upon admission, the proportion of patients with imported uncomplicated malaria and elevated liver enzymes was 128/186 (69%). In CHMI, 97/187 (52%) participants showed LFT abnormalities, including mild (64%, >1.0 ≤ 2.5× upper limit of normal (ULN)), moderate (20%, >2.5 ≤ 5.0xULN) or severe (16%, >5.0xULN). LFT abnormalities were primarily ALT/AST elevations and to a lesser extent γGT and ALP. LFT abnormalities peaked shortly after initiation of treatment, regardless of drug regimen, and returned to normal within three to six weeks. Positive associations were found with parasite burden and inflammatory parameters, including cumulative inflammatory cytokine responses and oxidative stress markers (r = 0·65, p = 0·008, and r = −0·63, p = 0·001, respectively). Interpretation This study shows that reversible liver injury is a common feature of uncomplicated falciparum malaria, most likely caused by an enduring pro-inflammatory response post treatment. The recognition of this phenomenon is of clinical relevance for individual patient care as well as clinical development of (new) antimalarial drugs. Fund PATH Malaria Vaccine Initiative (MVI)

Acute Kidney Injury during Malaria in Togolese Children

Objective: To describe clinical, biological and evolutionary profile of Acute Kidney Injury (AKI) due to Severe Malaria in the pediatric department. Methodology: This was a retrospective descriptive study that took place from January to December 2012. It has been included children aged 0 - 15 years admitted for severe malaria with positive thick drop. AKI was defined by using the modified RIFLE (Risk Injury Failure Loss End stage) classification for Pediatrics. Results: 338 children admitted for severe malaria were included. AKI was diagnosed in 24 children, a prevalence of 7.1% according to pRIFLE classification: RISK in 10 (3%), INJURY in 9 (2.6%) and FAILURE in 5 (1.5%). The average age was 8.16 ± 4.2 years. Clinical features were dominated by hemoglobinuria in 87.5%, oliguria, vomiting and fever in 75%. The biological features were dominated by severe anemia (Hb 5.5 mmol/l) was found in 2 cases. The mean parasitic density was 22,120 trophozoites. Malaria was treated primarily with artemether in 83.3% of the cases. Dialysis was indicated in 2 cases for menacing hyperkalaemia, but was not done because of lack of financial means. In one case, hyperkalaemia was successfully treated with symptomatic measures, but in the second case, these measures were not allowed to normalize kalaemia, and death occurred. Conclusion: Acute post-malarial renal failure secondary to tubular necrosis may be the dominant clinical features of severe malaria. Death may occur. Preventing malaria would be the best way to avoid it.

Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis

BackgroundThe 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.MethodElectronic 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.ResultsA 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).ConclusionThe 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.

Acute myocarditis in vivax malaria: an extremely rare complication

We report on the occurrence of pulmonary oedema due to acute myocarditis in an adolescent girl, from the northern Indian state of Uttarakhand, with Plasmodium vivax infection after parasite clearance. Apart from pancytopenia, there were no other features of severe malaria. With the emergence of literature about the complications encountered in P. vivax, especially from this region, a high index of suspicion for unusual cardiovascular manifestations is necessary in cases with acute malaria.

Polyuria in association with Plasmodium falciparum malaria in a region of unstable transmission

During a recent epidemic of Plasmodium falciparum malaria in Hlabisa district, KwaZulu Natal, polyuria was recognized in a subset of adults presenting to hospital with severe disease. In January to May 2000, following consent, cases of severe malaria provided blood spots for HIV testing, clinical data, and blood and urine samples for investigation of the polyuria. Four hundred and eleven adults with malaria were admitted, of whom 175 had severe malaria and 37 had polyuria (21% of severe cases). In those with polyuria the mean 24-h urine output was 3018 ml or 2.85 ml/kg/h. Ten of 15 (66%) patients investigated had urine and plasma osmolalities consistent with diabetes insipidus. There was no significant association between polyuria and sex, age, HIV status or features of severe malaria. Whether the polyuria in these non-immune adults is a localized problem unrelated to malaria, or a hitherto unrecognized complication of severe malaria is not clear. Physicians are alerted to this observation, and the need for more clinical and pathophysiological studies.

Paludisme grave avec hyperparasitémie, chez un nourrisson voyageur

Introduction. – Severe falciparum malaria is a polymorphous life-threatening disease. Hyperparasitemia is rare among non-immune children returning from tropical areas. Case report. – We report a case of an infant returning from Ivory Coast who presented with fever, prostration and marked thrombocytopenia (22 000 platelets/mm 3). Blood slide showed Plasmodium falciparum ring forms. Parasite density dramatically increased from 1.7% to 45%, and the child developed several features of severe malaria, according to WHO definition. Conclusion. – In this non-immune infant, prostration and thrombopocytopenia seemed to be earlier predictors of severity than hyperparasitemia and other WHO criteria, which have not been yet validated in travelling children.