The Role of Platelets in Malarial Acute Lung Injury and Acute Respiratory Distress Syndrome: A World of Possibilities.

In recent decades our understanding of platelets’ role in immune response has increased. Traditionally platelets were considered as bleeding-stopping and thrombosis-causing cells. In recent years the platelets’ role in malarial innate and adaptive immune responses is being recognized. Platelets play critical role in pathogenesis of malaria infection leading to variety of outcomes. It is being realized that platelets play dual role in case of malaria (i) by preventing early stage exponential growth of parasitemia (ii) promoting exaggerated immune responses later. Platelets role in pathogenesis of severe and cerebral malaria has been widely studied. However their role in malaria related acute lung injury and respiratory distress has gained less attention. Recently the presence of active megakaryocytes and proplatelets have been explained in human lungs. Simultaneously, the platelets role in pathogenesis of acute lung injury and respiratory distress (ALI/ARDS) was also recognized. This gives a hint that there is a possible association of platelets with malaria related respiratory diseases as well. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. In this review we have attempted to establish the importance of role of platelets in malaria related acute lungs injury and malaria acute respiratory distress syndrome and try to explain the underlying mechanism of this process. In ALI/ARDS, including those caused by malaria, platelets participate sequestration to the vascular bundle facilitating the recruitment of immune cells viz. neutrophils. Additionally, they secrete or induce the secretion of chemokines that result into vascular damage.

Sintomas neurológicos agudos e residuais na malária / Acute and residual neurological symptoms in malaria

A malária é a principal e a mais grave doença parasitária no mundo. A infecção pelo Plasmodium falciparum é capaz de afetar diretamente o sistema nervoso central, causando déficits cognitivos e comportamentais que caracterizam a malária cerebral (MC). A MC é uma complicação decorrente da malária grave sendo responsável pela maioria dos casos de incapacidade e óbito. A ocorrência de seqüelas cognitivas e comportamentais após tratamento da MC tem sido descrita, principalmente em crianças. Adultos e crianças apresentam diferenças nas manifestações clínicas resultantes da MC. Geralmente, as crianças cursam com um espectro maior de alterações e apresentam déficits em vários domínios cognitivos após o tratamento da doença. Apesar da sua relevância clínica, os mecanismos patogênicos envolvidos no desenvolvimento das seqüelas resultantes da MC permanecem pouco elucidados. O entendimento desses mecanismos é fundamental para elaboração de intervenções terapêuticas adequadas que atuem na prevenção desses transtornos.

Malaria is the main and most serious parasitic disease in the world. Plasmodium falciparum infection can affect directly the central nervoussystem leading to cognitive and behavioral impairment which characterize cerebral malaria (CM). CM is a complication of severe malaria beingresponsible for almost all disability and death. The occurrence of cognitive and behavioral impairment after treatment has been reported, especially in children. Adults and children have differences in clinical manifestations related to CM. In general, children tend to present a greater spectrum of symptoms and impairment in almost all domains of cognition after infection treatment. Despite of its clinical relevance, pathogenic mechanisms involved in the development of CM sequelae remain poorly understood. A better understanding of these mechanisms is essential for the elaboration of appropriate therapeutic interventions which may contribute to the prevention of CM sequelae.

Evaluation of alternative diagnostic techniques for diagnosis of cerebral malaria in a tertiary referral hospital in Bangladesh.

Five alternative techniques for diagnosis of malaria were evaluated in 124 clinically diagnosed cerebral malaria cases admitted in a tertiary hospital in Bangladesh. Clinical diagnosis of cerebral malaria was done by WHO criteria. The tests were conventional routine malaria microscopy; prolonged microscopy; dipstick antigen capture assay (Para Sight TM-F test); pigments in peripheral leucocytes and routine microscopy repeated at 12 hours interval. First four tests were done at 0 hours of hospital admission and repeat routine microscopy was added at 12 hours interval. Diagnostic capability of the test was 64%, 65%, 69%, 27% and 63% respectively. None of the tests except pigments in peripheral leucocytes was superior at initial evaluation. Only the dipstick test added 5% more diagnostic possibility compared with routine microscopy as standard. Stratification of diagnostic capability in different ways improved diagnosis 15% and 11% in smear negative cases by dipstick and prolonged microscopy respectively. It was increased by 50% (5/10 patients) with dipstick test in the smear negative patients with history of anti-malarials prior to hospital admission.

Pseudobulbar paralysis--a sequelae of cerebral malaria.

Demyelination may be a pathogenic mechanism of post-malarial neurological sequelae. It can cause pseudobulbar palsy, which has not been documented earlier. In the present communication we report two cases of pseudobulbar palsy after cerebral malaria with evidence of demyelination.

Cerebral malaria in Indian adults: a prospective study of 441 patients from Bikaner, north-west India.

AIMS OF THE STUDY: As per WHO (1993) the assessment and analysis of local problems and an appropriate epidemiological information system is an essential part of a control programme before embarking any control activity. METHODOLOGY: Four hundred and fourty one (441) adults of strictly defined admitted cerebral malaria patients were studied. Detailed clinical/neurological examination was done at the time of admission, daily thereafter, at the time of regaining consciousness, at the time of discharge and at weekly intervals in those having neurological sequelae. All patients were treated by i.v./oral quinine and specific syndromes were managed according to WHO guidelines. RESULTS: Apart from fever and unconsciousness in all the patients, other features were convulsion (21.31%), neck rigidity (19%), psychosis (5.21%), conjugate deviation of eyes (2.26%), extrapyramidal rigidity (2.25%), trismus (1.31%), decorticate rigidity (1.13%) and decerebrate rigidity (0.90%). One hundred forty five (32.87%) patients expired and mortality was highest in pregnant ladies (39.28%). The important neurological sequelae in survivors were psychosis in 15 (5.06%), cerebellar ataxia in 14 (4.72%), hemiplegia in five (1.68%), extrapyramidal rigidity (EPR) in four (1.35%), peripheral neuropathy in three (1.01%), EPR with trismus in one (0.33%) and isolated sixth nerve palsy in one (0.33%) patients and all showed complete recovery in further follow up. CONCLUSION: The important observations of this study were stormy presentation, increased incidence of haemoglobinuria and jaundice, presence of neck rigidity, no prognostic relation to fundus abnormalities and high incidence of cerebellar ataxia and psychosis as neurological sequelae in survivors. Knowledge of self-limiting course of neurological sequelae may be helpful in reducing economic strain of expensive investigations and treatment.

Brainstem auditory evoked potentials and somatosensory evoked potentials in cerebral malaria--a prognostic significance.

OBJECTIVE: To study the changes in brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SSEPs) in cerebral malaria and to see their prognostic significance. METHODS: BAEPs and right median nerve SSEPs were performed in 25 adult patients of strictly defined cerebral malaria in acute stage in a semi-dark, sound proof chamber on four channel computerized multi-basis OTE-Biomedica machine in department of neurology, SP Medical College, Bikaner. RESULTS: The abnormalities of BAEPs were delayed peak latency of wave III in 13/25 (52%) and wave V in 20/25 (80%) patients and delayed interpeak latencies (IPLs) of wave I-III in 9/25 (36%), wave I-V in 15/25 (60%) and wave III-V in 12/25 (48%) patients. In SSEPs delayed N20 was seen in 11/25 (44%); delayed IPLs of N13-N20 (central conduction time; CCT) in 12/25 (48%) patients. Distorted N20 was recorded in 12/25 (48%) patients. Both N13-N20 IPLs in SSEPs and wave III-V IPLs in BAEPs were delayed in five patients and all of them expired. Delayed N13-N20 with normal III-V IPLs was present in seven patients and two of them died, whereas delayed III-V IPLs with normal N13-N20 was present in seven patients, and one of them expired. In remaining six patients both the parameters were normal and one of them died. CONCLUSIONS: The values of BAEPs and SSEPs were abnormal in patients of cerebral malaria and it was observed that BAEPs/SSEPs alone was not useful for predicting the outcome of coma, whereas abnormalities in both was predictive of worst prognosis. The changes in evoked potentials (BAEPs and SSEPs) could be due to either interruption of conduction in central pathways because of structural changes due to petechial hemorrhages and malarial granuloma at multiple levels in the brain including brainstem or due to metabolic abnormalities.

Pleural effusion in childhood falciparum malaria.

Pulmonary complication is a rare manifestation of childhood malaria and isolated pleural effusion without pulmonary edema has never been reported in children. We report here an 11-year-old boy who suffered from cerebral malaria and massive right pleural effusion. The patient was treated with intravenous artesunate, albumin, and other supportive treatments. He recovered completely after eight days. The clinical and laboratory courses suggested that the plasma leakage played a role in the pathogenesis of pleural effusion.

Levels of serum tumor necrosis factor alpha in relation to clinical involvement and treatment among Thai adults with Plasmodium falciparum malaria.

Concentrations of tumor necrosis factor alpha (TNF-alpha) in serum were measured in 17 Thai men infected with Plasmodium falciparum malarial infections to determine whether they were affected by severity of infections or exchange transfusions. Twelve patients were considered having complicated malarial infections, eight of whom had cerebral malaria. Five patients had uncomplicated malarial infections. The results showed that malarial infection markedly raised TNF-alpha level above normal values (mean +/- SEM 406 +/- 38 vs 15 +/- 5, p = 0.004). In complicated malaria, cerebral involvement appeared to significantly increase concentration of TNF-alpha when compared to values in uncomplicated malaria (mean +/- SEM 496 +/- 64 vs 339 +/- 12, p = 0.01). Degree of parasitemia, intravenous quinine (day 0 value vs day 7 value) and exchange transfusion did not significantly affect TNF-alpha levels. Conclusion: Serum level of TNF-alpha is increased in Plasmodium falciparum malarial infections and may be a useful index to predict severity of malarial infection, cerebral malaria in particular.

Incidence and outcome of neurological sequelae in survivors of cerebral malaria.

This hospital based study was carried out on 185 adult patients of cerebral malaria. Out of 185 patients, 62 (33.5%) died and 123 (66.5%) survived. Neurological sequelae were present in 13 (10.5%) of 123 survivors at the time of discharge (i.e. 10-15 days after recovery from coma) from the hospital. These were in form of psychosis in 5 patients (4%), cerebellar ataxia in 4 patients (3.2%), extrapyramidal rigidity in 2 patients (1.62%) and hemiplegia in 2 patients (1.62%).

Imported cerebral malaria complicated with glucose 6 phosphate dehydrogenase deficiency

Two cases of cerebral malaria imported from Guyana and Ghana are reported. These are the first cases of cerebral malaria diagnosed and treated in Trinidad and Tobago since malaria was eradicated. The management of both these cases was complicated because the patients' erythrocytes were glucose-6-phosphate dehydrogenase-deficient, and by the occurrence of blackwater fever, cerebral manifestations, renal impairment, hyperglycaemia and thrombocytopenia. The symptoms of cerebral malaria resolved following treatment with quinidine and doxycycline and quinidine and clindamycin.

Malária cerebral e AIDS: relato de caso / Cerebral malaria and AIDS: case report

Embora nao esteja definitivamente comprovada que a severidade da malária esteja associada com o vírus da imunodeficiência humana (HIV), sabe-se que a infecçao pelo Plasmodium falciparum pode favorece uma rápida evoluçao da infecçao pelo HIV. Além disso a associaçao da malária com HIV/AIDS, do ponto de vista clínico, pode ser extremamente grave face a ocorrência de outros microorganismos e/ou neoplasias, o que piora a evoluçao e prognóstico dos pacientes. A concomitância do vírus HIV com o Plasmodium em zonas endêmicas de malária, é uma possibilidade que deve ser sempre pensada, visto que a sua transmissao está relacionada a fatores de risco ligados aos comportamentos das pessoas, que nem sempre sao logo revelados e/ou identificados. Os autores descrevem um caso de malária cerebral Plasmodium vivax e Plasmodium falciparum em um paciente com AIDS. Descrevem sua evoluçao clínica e terapêutica.

Malaria cerebral en niños: experiencia en Honduras y revisión de la literatura / Cerebral malaria in children: Honduran experience and review

La malaria cerebral puede producir gran variedad de síntomas y signos. Presentamos 14 casos diagnósticados en el Hospital Regional del Sur y en el bloque Materno Infantil del Hospital Escuela, Honduras, de agosto de 1970 a mayo de 1995. Los pacientes se presentaron con síntomas y signos de encefalopatía aguda con conducta psicótica, convulsiones y fiebre. La malaria cerebral debida a Plasmodium vivax ocurrió en 71//de los casos. Todos los pacientes fueron tratados con cloroquina y en 12 casos también con primaquina. Dos pacientes fueron tratados con amodiaquina. Dos pacientes murieron, uno con daño cerebral severo y otro con hipovolémico más neumonía bilateral

Electroencephalography in cerebral malaria.

Electroencephalography (EEG) was performed in 13 male patients with cerebral malaria during the first 24 hours of admission, using a 10-channel, 10-20 system EEG machine (6 montages, 20 minute duration). The EEG patterns were of theta and delta waves from both sides of cerebral hemisphere suggesting diffused cortical dysfunction. No epileptic pattern was found in patients who had seizures prior to, or after admission. The initial EEG performed on the day of admission did not show any specific pattern attributable to any pathological condition. It was also unable to predict the prognosis of the 2 dead patients. However, one cerebral malaria patient with left hemiplegia was subsequently found to have right basal ganglia hemorrhage in CAT scan, high amplitude delta waves and theta waves in the tracings of the right hemisphere. The study suggests that a single EEG data on admission can hardly give enough information for prediction of the clinical course and outcome of cerebral malaria. Serial EEGs probably provide more useful information regarding the prognostic signs in this group of patients. Nevertheless, EEG could be useful to rule out some cerebral pathology such as space occupying lesions, epilepsy or any other causes of unconsciousness that could produce similar cerebral symptoms in malaria patients.