Amount of Brain Edema Correlates With Neurologic Recovery in Pediatric Cerebral Malaria.

BACKGROUND: Cerebral malaria (CM) remains a leading cause of mortality and morbidity in children in sub-Saharan Africa. Recent studies using brain magnetic resonance imaging have revealed increased brain volume as a major predictor of death. Similar morphometric predictors of morbidity at discharge are lacking. The aim of this study was to investigate the utility of serial cranial cisternal cerebrospinal fluid (CSF) volume measurements in predicting morbidity at discharge in pediatric CM survivors. METHODS: In this case-control study, 54 Malawian pediatric CM survivors with neurologic sequelae evident at discharge who underwent serial magnetic resonance imaging scans while comatose were matched to concurrently admitted children with serial imaging who made full recoveries. Serial cranial cisternal CSF volume quantified by radiologists blinded to outcome was evaluated as a predictor of neurologic deficits at discharge. The probability of neurologic sequelae was determined using a model that included coma duration and changes in cisternal CSF volume over time. RESULTS: Coma duration before admission was similar between cases and controls (16.1 vs. 15.3; P = 0.81), but overall coma was longer among children with sequelae (60 vs. 38 hours; P < 0.01). Lower initial CSF volumes and decreased volumes over time were both associated with a higher probability of neurologic sequelae at discharge. CONCLUSIONS: Among pediatric CM survivors with prolonged coma, lower initial CSF volume and decreasing volume during coma is associated with neurologic sequelae at discharge. These findings suggest that cerebral edema is an underlying contributor to both morbidity and mortality in pediatric CM.

IMPORTED TROPICAL MALARIA (CASE REPORT).

Malaria is a parasitic disease. It is one of blood infections caused by malaria plasmodia. The disease is transmitted to a human by a bite of a female mosquito of Anopheles genus. Local malaria transmission in Ukraine has not been registered since 1956, however, every year some imported cases occur. In 2017, 45 cases of malaria were imported to Ukraine: 80% of them were caused by P. falciparum. The aim of the research is to present a case of imported tropical malaria in a pregnant woman with the development of malaria coma. An unusual course of the illness made diagnoses difficult due to partial immunity of the patient caused by multiple previous invasions of malaria plasmodia. The diagnosis was confirmed by blood microscopy. A literature on epidemiology, clinical findings and current tropical malaria course has been scanned as well. In the presence of an appropriate epidemiological anamnesis, the patients with fever of unknown genesis should first of all be examined for malaria, the most socially significant tropical disease. It is necessary to define the type of malarial plasmodium by repeated blood parasitoscopy by a thick-blood film and blood smear coloured by Gimza-Romanovsky method. Doctors' vigilance against malaria allows preventing complicated forms and late relapses of this malignant invasion. The countries free of malaria can also face this problem and therefore they should be ready to diagnose and treat this disease effectively. The infectious diseases hospitals of Ukraine should be supplied with antimalarial drugs.

A case of Naegleria fowleri related primary amoebic meningoencephalitis in China diagnosed by next-generation sequencing.

BACKGROUND: Primary amoebic meningoencephalitis (PAM), caused by Naegleria fowleri, is a rare protozoan infectious disease in China. A fatality rate of over 95% had been reported due to extremely rapid disease progression in the USA and other countries. Rapid and precise identification of the causative agent is very important to clinicians for guiding their choices for administering countermeasures in the clinic. In this report, we applied the next-generation sequencing (NGS) method to rapidly show that N. fowleri was the causative agent of a fatal case involving a 42-year-old man with severe PAM disease, the first reported in mainland China. CASE PRESENTATION: A 42-year old male in a deep coma was admitted to Shenzhen Third People's Hospital, a special medical care unit with expertise in infectious diseases. Increased intracranial pressure was detected. The cerebrospinal fluid (CSF) sample was found to be red and cloudy with increased leukocyte and protein levels. While bacterial cultures with CSF were negative, N. fowleri was determined to be the causative agent with NGS. Amphotericin B (AmB), a drug with anti-amoeba activity, was used immediately, but the treatment came too late and the patient died 2 days after the NGS confirmation. CONCLUSION: In this paper, we reported a case of PAM disease for the first time in mainland China. NGS was used for rapid diagnosis and provided guidance for prescribing medications. However, the patient died due to a late admission amid advanced PAM disease. Early detection of N. fowleri is necessary in order to select effective drug treatments and control the disease progression. Despite the negative survival outcome, NGS was shown to be a promising method of rapid and precise identification of N. fowleri.

Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria.

BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren's Children's Hospital were quantified and used for comparison. RESULTS: Children with CM had significantly higher CSF concentration of kynurenine and KYNA than Swedish children (P < 0.0001 for both), and CSF kynurenine and KYNA were positively correlated. In children with CM, CSF kynurenine and KYNA concentrations were associated with coma duration in children of all ages (P = 0.003 and 0.04, respectively), and CSF kynurenine concentrations were associated with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month follow-up in children ≥5 years old. CONCLUSIONS: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of attention and cognition.

Hemiparesis post cerebral malaria.

Cerebral malaria is one of the most serious complications in the Plasmodium falciparum infection. In endemic areas, the cerebral malaria interested mainly children. The occurrence in adults is very rare and most interested adult traveling in tropical zones. This case report describes a motor deficit post cerebral malaria in a young adult traveling in malaria endemic area. This complication has been reported especially in children and seems very rare in adults.

A severe case of rat lungworm disease in Hawa'i.

A 23-year-old man living on the island of Hawa'i developed a life threatening case of eosinophilic meningitis caused by infection with Angiostrongylus cantonensis (rat lungworm disease: RLWD). He was comatose for 3 months, incurring brain and nerve damage sufficiently extensive that he was not expected to recover. The case was complicated by secondary infections of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and pneumonia, which resulted in an empyema requiring a thoracoscopy and decortication. He was treated with prednisone, mebendozal, and pain medication for RLWD, and antibiotics and antifungal medications for the secondary infections. The administration of herbal supplements was requested by the family and approved, and these were administered through a gastric tube. Less than a month after being declared in a persistent vegetative state the man was able to talk, eat, and had regained some muscle functions. After release from the hospital he continued the use of supplements and received treatments of intravenous vitamin therapy. Four years after onset of the illness he is able to ride a bicycle, is a part time student, plays guitar, and is fluent in two foreign languages. RLWD is an emerging tropical disease of growing importance in Hawa'i.

Efficacy of Quinine versus Artemether in the treatment of severe malaria.

BACKGROUND: For centuries Quinine has been used as very effective antimalarial drug and with advent of Artemisinin and its derivative Artemether there stands a concern about the superiority among these drugs especially in case of severe malaria in paediatric population. This study compares these drugs to explore their effectiveness. METHODS: A randomized prospective study was conducted with a view to compare efficacy regarding fever clearance, parasitaemia clearance and coma resolution between Quinine (10 milligrams per kilogram per dose diluted in 100 ml of 10 % dextrose solution T.D.S for seven days) and Artemether (3.2 milligrams per kilogram per day I.M on the first day and 1.6 milligrams per kilogram per day from second to fifth day of treatment) among 138 children with severe malaria in Bolan Medical College, Quetta, Pakistan. Study was conducted from December 2009 to December 2011. Ethical clearance was taken from Ethical clearance committee, Bolan Medical College, Quetta, Pakistan. RESULTS: Parasitaemia clearance was better with Artemether than Quinine. Parasitaemia clearance was 68 (98.55%) and 69 (100%) on third and fifth day respectively in Artemether group while Quinine group had 64 (92.75%) and 67 (97.1%) on third and fifth day respectively [third day [RR=0.9412 (95%CI, 0.8759-1.0113) P=0.2084 and fifth day respectively [RR=0.9571 (95%CI 0.9109-1.0058) P=0.2446]. Between 24-72 hours the coma recovery rate for Quinine and Artemether were 49 (98%) and 41 (85.41%) respectively [RR=1.1473 (95%CI 1.0141-1.298) P=0.029203 but after 72 hours of treatment the coma recovery remained 49 (98%) for quinine while it was 42 (87.5%) for artemether; RR=1.12 (95%CI 0.9993-1.2553) P=0.0568. The rapid resolution of coma with Quinine within 24 to 72 hours and after 72 hours were statistically significant than Artemether. CONCLUSIONS: In severe paediatric malaria intravenous Quinine or intramuscular Artemether therapy does not have any statistically significant difference in terms of fever clearance but Quinine has statistically significant shorter duration of coma resolution than with Artemether therapy after 24 hours of treatment.

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response.

BACKGROUND: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-ß levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. CONCLUSIONS: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value.

Hydatid cyst of the ambient cistern radiologically mimicking an arachnoid cyst.

Hydatid cysts of the posterior fossa are extremely rare. Intracranial hydatid cysts are more common in children and occur more frequently in the supratentorial space. A 7-year-old boy was admitted to the emergency department because of intense headache, nausea, vomiting, and progressive drowsiness that developed within the period of a week. On radiological examination a round, 2.5 × 2.5-cm cystic lesion appeared in the ambient cistern and caused hydrocephalus as a result of extrinsic aqueductal stenosis. The cyst was successfully removed using the puncture, aspiration, irrigation, and resection technique via an infratentorial-supracerebellar approach with the patient in the sitting position. The authors here described an unusual case of a hydatid cyst in the left ambient cistern with hydrocephalus due to extrinsic aqueductal stenosis, which seems to be the first such case in the literature. Hydatid cyst may be considered in the differential diagnosis of arachnoid cysts of the quadrigeminal cistern to determine which surgical procedure to perform and to avoid unexpected complications.

Children with retinopathy-negative cerebral malaria: a pathophysiologic puzzle.

BACKGROUND: Cerebral malaria, defined as otherwise unexplained coma in a patient with circulating parasitemia, is a common disease in the developing world. The clinical diagnosis lacks specificity and children with other underlying causes of coma might be misdiagnosed as having cerebral malaria. The presence of malarial retinopathy can be used to differentiate children whose comas are caused by Plasmodium falciparum and its attendant pathophysiologies from those with other reasons for their abnormal mental status. Children with cerebral malaria who lack malarial retinopathy have not previously been described. METHODS: All patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi, during a 12-month period with a clinical diagnosis of cerebral malaria were evaluated for the presence of malarial retinopathy. Thirty-two patients lacked retinopathy findings. Clinical, laboratory, and radiologic information data were collected. RESULTS: Thirty-two cases of retinopathy-negative cerebral malaria are presented. CONCLUSIONS: Children with retinopathy-negative cerebral malaria share a common clinical phenotype with lower rates of mortality compared with those who have malarial retinopathy. There are at least 4 possible pathophysiologic explanations for this common condition.

Is human malarial coma caused, or merely deepened, by sequestration?

Much research into falciparum malaria coma assumes the primary event to be vascular obstruction by parasitized red blood cells. Recent evidence that vivax malaria, caused by a parasite traditionally thought not to block blood flow, seems to alter brain function to the same degree as falciparum malaria has seriously questioned this. These data are a timely call to reassess whether vascular obstruction should still be considered the primary cause of the coma of falciparum disease. They add to a growing literature that suggests that enhancement of brain-origin cytokines, such as tumour necrosis factor, by non-brain systemic inflammation and an appreciation of the degree to which neuronal homeostasis depends on them provide a more fruitful research direction.

Cerebral malaria in children with cyanotic heart diseases: the need for a closer look.

We report four cases of encephalopathy admitted with fever, hypercyanosis, breathlessness, deep coma and convulsions considered of interest because these children had cyanotic heart diseases and concomitant cerebral malaria. Their presenting clinical features, which suggested cerebral malaria (decreased level of consciousness ranging in severity from drowsiness and severe headache to confusion, delirium and even deep coma) may equally characterise hypercyanotic episodes among children with uncorrected cyanotic cardiac defects. We also inferred that children with cyanotic cardiac defects may be prone to cerebral malaria and that those residing in the tropics may benefit from anti-malarial prophylaxis.

Blood coagulation, inflammation, and malaria.

Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic system; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article (i) reviews the literature related to blood coagulation and malaria in a historic perspective, (ii) describes basic mechanisms of coagulation, anticoagulation, and fibrinolysis, (iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), (iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falciparum infected patients, and (v) emphasizes the procoagulant role of parasitized red blood cells (RBCs) and activated platelets in the pathogenesis of malaria. This article also presents the Tissue Factor Model (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell (EC) activation, blood coagulation disorder, and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis.

Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response.

We describe 2 spatially distinct foci of human African trypanosomiasis in eastern Uganda. The Tororo and Soroti foci of Trypanosoma brucei rhodesiense infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and host-immune response. In particular, infections with the Tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage and higher plasma interferon (IFN)- gamma concentration, compared with those with the Soroti genotype. We propose that the magnitude of the systemic IFN- gamma response determines the time at which infected individuals develop central nervous system infection and that this is consistent with the recently described role of IFN- gamma in facilitating blood-brain barrier transmigration of trypanosomes in an experimental model of infection. The identification of trypanosome isolates with differing disease progression phenotypes provides the first field-based genetic evidence for virulence variants in T. brucei rhodesiense.

The distribution and intensity of parasite sequestration in comatose Malawian children.

BACKGROUND: The sequestration of Plasmodium falciparum-infected erythrocytes in capillary beds is a characteristic feature of severe malaria and is believed to be central to disease pathogenesis. Sequestration occurs in all P. falciparum infections, including those in asymptomatic individuals. Therefore, sequestration cannot be the sole determinant of severe disease; the intensity or distribution of infected erythrocytes may also contribute. Discerning the relationship between sequestration and well-defined clinical syndromes may enhance understanding of disease mechanisms. METHODS: We measured the concentration of parasite-derived lactate dehydrogenase (pLDH) in tissue samples obtained at autopsy from patients with clinically defined cerebral malaria. On the basis of the autopsy findings, patients were divided into 2 groups: those with an identifiable, nonmalarial cause of death and those without, who were presumed to have died of cerebral malaria. The concentration of pLDH, as determined by enzyme-linked immunosorbent assay, was used to estimate parasite load in different organs. RESULTS: When pLDH could be detected, the parasite load was higher in patients with presumed cerebral malaria than in parasitemic patients with assumed cerebral malaria with a nonmalaria cause of death identified at autopsy (P<.05 for brain, intestine, and skin). CONCLUSIONS: These findings suggest that sequestration in patients with fatal cerebral malaria occurs in multiple organs and does not reflect a predilection in the parasite for the cerebral vasculature.

Household decision-making process and childhood cerebral malaria in The Gambia.

Mortality from childhood cerebral malaria remains unacceptably high in endemic regions. This survey was conducted between June and December 2001 among 69 primary caregivers of children admitted for cerebral malaria in Bansang Hospital, Central River Division (CRD), The Gambia to describe decision-making process at the family level that could have impact on malaria mortality. Thirty two percent of children presented in coma after 24 h of onset of illness. The eldest person in the compound or the father was responsible for taking decision on when hospital treatment was necessary in 85% of the cases. Mothers who were the primary caregivers made such decisions only in 7% of the cases. Cultural norms in a community are important factors affecting preferences at the household level and could influence important medical decisions. This survey suggests that patriarchs and/or fathers are important target groups for health education and project implementation programs.

Pattern of cerebral malaria in children at the Lagos University Teaching Hospital.

UNLABELLED: Cerebral malaria is one of the most lethal forms of malaria. Given that malaria is a constantly evolving disease, it is therefore necessary to document patterns of presentation even in the same centre over a period of time. OBJECTIVE: To document the prevalence and pattern of cerebral malaria in children. DESIGN: Cross-sectional descriptive study of children with cerebral malaria attending the emergency room of the Lagos University Teaching Hospital. Age, sex, month at which diagnosis was made, associated clinical features, condition at discharge and mortality were assessed. RESULTS: Cerebral malaria was documented in 107/3309 (3.2%) children. There was an equal male:female ratio. Cerebral malaria occurred most frequently between July and September and in children between 2 and 2.9 years. A total of 79/107 (73.8) recovered fully at discharge, 9/107 (8.4%) recovered with some neurological sequelae while 19/107 (17.8%) died. Coma score on admission was significantly lower among those who died compared with those who survived (p = 0.001). Clinical signs observed in these children were seizures-88/107 (82.2%), pallor-75/107 (70.1%), jaundice-55/107 (51.4%) and hepato-splenomegaly-18 (16.8%). However, decerebrate posturing was the only clinical sign associated with a fatal outcome OR, 11.47 (p = 0.009). CONCLUSION: This study shows that cerebral malaria still remains a problem of the under fives with unacceptably high mortality. The clinical significance of decerebrate posture as an indicator of mortality would require further evaluation.

Severe anaemia in childhood cerebral malaria is associated with profound coma.

BACKGROUND: Severe anaemia in children with cerebral malaria has been associated with respiratory distress secondary to lactic acidosis and/or hypoxia. The ensuing metabolic derangement may further depress the level of consciousness culminating in presentation with profound coma. This association has poorly been studied. OBJECTIVE: To determine the relationship between profound coma at presentation and the presence of severe anaemia in children with cerebral malaria. METHODS: This cross-sectional study involved 100 children with cerebral malaria who were consecutively recruited at admission in the Paediatric emergency unit of Mulago hospital in Uganda from July to December 2000. Clinical and laboratory evaluation was done using the hospital's guidelines for the management of severe malaria. The exposure factor of interest was severe anaemia (Hb < 5.0 g/dl) and occurrence of profound coma (Blantyre coma Scale 0) was the outcome measure. RESULTS: Severe anaemia and profound coma were seen in 20% and 9% of the children respectively. Severe anaemia was independently associated with profound coma, adjusted OR 1.34 (CI 1.17 - 1.95), p = 0. 002 and age < 3 years, adjusted OR 1.42 (CI 1.13 - 1.54), p = 0.001). Thirty percent of those with severe anaemia had deep sighing (acidotic) breathing compared to only 15% of those with haemoglobin (Hb) > 5 g/dl, OR 1.21 (CI 0.90 - 1.64), p = 0.118. There was no association between the malaria parasite density and severe anaemia. A similar proportion of those with severe anaemia regained consciousness within 24 hours compared to those with Hb > 5 g/dl (30 vs 42.5%), OR 1.56 (0.65 - 3.71), p = 0.307. CONCLUSIONS: The findings suggest that profound coma in cerebral malaria may not only result from primary malaria encephalitis but possibly also from a metabolic dysfunction due to severe anaemia.

Clinics in diagnostic imaging (58). Chronic cerebral paragonimiasis.

A 36-year-old Korean man presented with a history of epilepsy. MR imaging of the brain revealed multiple conglomerated round nodules that were hypointense on both T1-and-T2 weighted images. These were located at the left temporal and occipital lobes and had surrounding encephalomalacia. CT scan confirmed the presence of large calcified nodules in the corresponding regions. These imaging findings were typical of chronic cerebral paragonimiasis. The clinical, CT and MR features of cerebral paragonimiasis are reviewed.