Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria.

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil. Peripheral blood smears, ECG, and bedside echocardiography were conducted before antimalarial treatment and repeated at follow-up after completed treatment. We evaluated the diagnostic value of PR-segment depression, PR-segment elevation, and Spodick's sign for detecting pericardial effusion. A subset of patients underwent Holter monitoring at baseline. Among 98 cases of uncomplicated malaria (55% men; mean age 40 years; median parasite density 1,774/µl), 75 had Plasmodium vivax, 22 Plasmodium falciparum, and 1 had mixed infection. At baseline, 17% (n = 17) had PR-segment depression, 12% (n = 12) PR-segment elevation, 3% (n = 2) Spodick's sign, and the prevalence of pericardial effusion was 9% (n = 9). ECG alterations had sensitivities of 22% to 89% and specificities of 88% to 100% for detecting pericardial effusion at baseline. PR-segment depression had the best accuracy (sensitivity 89%, specificity 90%). Of the 25 patients, 4 patients who did not have pericardial effusion, displayed nonsustained ventricular tachycardia, determined by Holter monitoring (median duration 43 hours). Follow-up examination data were obtained for 71 patients (median 31 days), for whom PR-segment depression, elevation, and pericardial effusion had reduced significantly (p <0.05). In conclusion, our findings suggest that ECG alterations may be useful to detect pericardial effusion in malaria and that these findings decrease after completed antimalarial treatment.

Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients.

Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study, we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses, and ex vivo assays. Patterns of clinical features, parasite burden, and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation, and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients' signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia, and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, particularly in the haematopoietic niche of bone marrow and spleen.

Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin.

BACKGROUND: Information on cardiopulmonary complications in clinical malaria is sparse and diagnosis may be difficult in resource-limited areas due to lack of proper diagnostic tools and access to medical care. A case of pericardial effusion and pulmonary alterations assessed by ultrasound in a patient with uncomplicated mixed malaria infection is described. CASE PRESENTATION: A previously healthy 23-year-old male from the Amazon Basin was diagnosed with mixed infection of Plasmodium vivax and Plasmodium falciparum by peripheral blood smear. The patient presented with mild malaria symptoms without signs of severe malaria, but reported moderate chest pain and shortness of breath. Laboratory analyses revealed thrombocytopenia and anemia. The electrocardiogram had PR depressions and bedside ultrasound of the cardiopulmonary system showed pericardial effusion (18 mm) accompanied by multiple B-lines in the lungs, identified as vertical artifacts extending from the pleural line. Cardiac biomarkers were normal. The patient was treated according to national guidelines for malaria and suspected pericarditis, respectively. At follow-up on day 5, the pericardial effusion (9mm) and B-lines had markedly decreased. By day 21 the patient was asymptomatic, had completed the treatment, and the electrocardiogram and ultrasound findings had normalized. CONCLUSIONS: This case report highlight the usefulness of bedside ultrasound to identify cardiopulmonary involvement in patients with uncomplicated malaria and relevant symptoms.

Plasmodium vivax Infection Alters Mitochondrial Metabolism in Human Monocytes.

Monocytes play an important role in the host defense against Plasmodium vivax as the main source of inflammatory cytokines and mitochondrial reactive oxygen species (mROS). Here, we show that monocyte metabolism is altered during human P. vivax malaria, with mitochondria playing a major function in this switch. The process involves a reprograming in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation. P. vivax infection results in dysregulated mitochondrial gene expression and in altered membrane potential leading to mROS increase rather than ATP production. When monocytes were incubated with P. vivax-infected reticulocytes, mitochondria colocalized with phagolysosomes containing parasites representing an important source mROS. Importantly, the mitochondrial enzyme superoxide dismutase 2 (SOD2) is simultaneously induced in monocytes from malaria patients. Taken together, the monocyte metabolic reprograming with an increased mROS production may contribute to protective responses against P. vivax while triggering immunomodulatory mechanisms to circumvent tissue damage. IMPORTANCE Plasmodium vivax is the most widely distributed causative agent of human malaria. To achieve parasite control, the human immune system develops a substantial inflammatory response that is also responsible for the symptoms of the disease. Among the cells involved in this response, monocytes play an important role. Here, we show that monocyte metabolism is altered during malaria, with its mitochondria playing a major function in this switch. This change involves a reprograming process in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation. The resulting altered mitochondrial membrane potential leads to an increase in mitochondrial reactive oxygen species rather than ATP. These data suggest that agents that change metabolism should be investigated and used with caution during malaria.

Epidemiology, drug resistance, and pathophysiology of Plasmodium vivax malaria.

Malaria, caused by the protozoan parasites of the genus Plasmodium, is a major health problem in many countries of the world. Five parasite species namely, Plasmodium falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi, cause malaria in humans. Of these, P. falciparum and P. vivax are the most prevalent and account for the majority of the global malaria cases. In most areas of Africa, P. vivax infection is essentially absent because of the inherited lack of Duffy antigen receptor for chemokines on the surface of red blood cells that is involved in the parasite invasion of erythrocytes. Therefore, in Africa, most malaria infections are by P. falciparum and the highest burden of P. vivax infection is in Southeast Asia and South America. Plasmodium falciparum is the most virulent and as such, it is responsible for the majority of malarial mortality, particularly in Africa. Although, P. vivax infection has long been considered to be benign, recent studies have reported life-threatening consequences, including acute respiratory distress syndrome, cerebral malaria, multi-organ failure, dyserythropoiesis and anaemia. Despite exhibiting low parasite biomass in infected people due to parasite's specificity to infect only reticulocytes, P. vivax infection triggers higher inflammatory responses and exacerbated clinical symptoms than P. falciparum, such as fever and chills. Another characteristic feature of P. vivax infection, compared to P. falciparum infection, is persistence of the parasite as dormant liver-stage hypnozoites, causing recurrent episodes of malaria. This review article summarizes the published information on P. vivax epidemiology, drug resistance and pathophysiology.

Distinct inflammatory profile underlies pathological increases in creatinine levels associated with Plasmodium vivax malaria clinical severity.

BACKGROUND: Although Plasmodium vivax infection is a frequent cause of malaria worldwide, severe presentations have been more regularly described only in recent years. In this setting, despite clinical descriptions of multi-organ involvement, data associating it with kidney dysfunction are relatively scarce. Here, renal dysfunction is retrospectively analyzed in a large cohort of vivax malaria patients with an attempt to dissect its association with disease severity and mortality, and to determine the role of inflammation in its progression. METHODS: A retrospective analysis of a databank containing 572 individuals from the Brazilian Amazon, including 179 patients with P. vivax monoinfection (161 symptomatic malaria, 12 severe non-lethal malaria, and 6 severe lethal disease) and 165 healthy controls, was performed. Data on levels of cytokines, chemokines, C-reactive protein (CRP), fibrinogen, creatinine, hepatic enzymes, bilirubin levels, free heme, and haptoglobin were analyzed to depict and compare profiles from patients per creatinine levels. RESULTS: Elevated creatinine levels were found predominantly in women. Vivax malaria severity was highly associated with abnormal creatinine increases, and nonsurvivors presented the highest values of serum creatinine. Indication of kidney dysfunction was not associated with parasitemia levels. IFN-γ/IL-10 ratio and CRP values marked the immune biosignature of vivax malaria patients, and could distinguish subjects with elevated creatinine levels who did not survive from those who did. Patients with elevated serum creatinine or severe vivax malaria displayed indication of cholestasis. Biomarkers of hemolysis did not follow increases in serum creatinine. CONCLUSION: These findings reinforce the hypothesis that renal dysfunction is a key component in P. vivax malaria associated with clinical severity and mortality, possibly through intense inflammation and immune imbalance. Our study argues for systematic evaluation of kidney function as part of the clinical assessment in vivax malaria patients, and warrants additional studies in experimental models for further mechanism investigations.

Cognitive performance of children living in endemic areas for Plasmodium vivax.

BACKGROUND: The role of repeated episodes of malaria on the cognitive development of children is a relevant issue in endemic areas since it can have a long-lasting impact on individual lifespan. The aim of the current paper was to investigate whether the history of malaria can impair the verbal and performance skills of children living in an endemic area with low transmission of Plasmodium vivax malaria. METHODS: A cross-sectional study was conducted with children living in an endemic area of P. vivax malaria in Brazilian Amazon basin. The history of episodes of malaria was used as criteria for inclusion of children in the groups. The cognitive performance was assessed by the Wechsler intelligence scale for children-III edition (WISC-III), which was applied to the participants of study by two trained psychologists. RESULTS: A total of 17 cases and 26 controls was included in the study. A significant low score of verbal quotient was found in the cases (p = 0.005), however, the performance IQ was similar in both groups (p = 0.304). The full-scale IQ was significantly lower in the cases when compared to the controls (p = 0.042). The factorials index showed significant difference only in the subtest of verbal comprehension with the lower values in the cases (p = 0.0382), compared to the controls. The perceptual organization (p = 0.363), freedom from distractability (p = 0.180) and processing speed (p = 0.132) were similar in both groups. CONCLUSIONS: Children with a history of vivax malaria has a significant impairment of verbal and full-scale quotients as well as a significant low index of verbal comprehension. These findings are likely due to the absenteeism caused by malaria and by the low parental education, which impairs an adequate response to the environmental stimulus.

Association between anthropometry-based nutritional status and malaria: a systematic review of observational studies.

BACKGROUND: Multiple studies in various parts of the world have analysed the association of nutritional status on malaria using anthropometric measures, but results differ due to the heterogeneity of the study population, species of the parasite, and other factors involved in the host and parasite relationship. The aim of this study was to perform a systematic review on the inter-relationship of nutritional status based on anthropometry and malarial infection. METHODS: Two independent reviewers accessed the MEDLINE and LILACS databases using the same search terms related to malaria and anthropometry. Prospective studies associating anthropometry and malaria (incidence or severity) were selected. References from the included studies and reviews were used to increase the review sensitivity. Data were extracted using a standardized form and the quality of the prospective studies was assessed. Selected articles were grouped based on exposures and outcomes. RESULTS: The search identified a total of 1688 studies: 1629 from MEDLINE and 59 from LILACS. A total of 23 met the inclusion criteria. Five additional studies were detected by reading the references of the 23 included studies and reviews, totaling 28 studies included. The mean sample size was 662.1 people, ranging from 57 to 5620. The mean follow-up was 365.8 days, ranging from 14 days to 1 year and 9 months, and nine studies did not report the follow-up period. Prospective studies assessing the relationship between malaria and malnutrition were mostly carried out in Africa. Of the 20 studies with malarial outcomes, fifteen had high and five had average quality, with an average score of 80.5 %. Most anthropometric parameters had no association with malaria incidence (47/52; 90.4 %) or parasite density (20/25; 80 %). However, the impact of malnutrition was noted in malaria mortality and severity (7/17; 41.2 %). Regarding the effects of malaria on malnutrition, malaria was associated with very few anthropometric parameters (8/39; 20.6 %). CONCLUSIONS: This systematic review found that most of the evidence associating malaria and malnutrition comes from P. falciparum endemic areas, with a significant heterogeneity in studies' design. Apparently malnutrition has not a great impact on malaria morbidity, but could have a negative impact on malaria mortality and severity. Most studies show no association between malaria and subsequent malnutrition in P. falciparum areas. In Plasmodium vivax endemic areas, malaria was associated with malnutrition in children. A discussion among experts in the field is needed to standardize future studies to increase external validity and accuracy.

Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia.

BACKGROUND: A large-scale study was set up in order to study the epidemiology, clinical aspects, and immunopathology of gestational and placental malaria in north-west Colombia. In this region, recent reports using a qPCR technique, confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax, up to 45%. Given the high rates of infection observed both in mother and placenta, a first exploratory study was proposed in order to characterize the effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp. infected placentas. METHODS: A descriptive, prospective, cross-sectional design was applied to pregnant women with (PM+) and without (PM-) placental malaria. Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines IL-2, IL-4, IL-10, IFN-γ and TNF, were measured in peripheral and placental blood using a quantitative PCR. The percentage of apoptotic cells was determined with a TUNEL assay. RESULTS: In total 50 placentas were studied: 25 were positive for submicroscopic infection and 25 were negative for Plasmodium infection. Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while IL-2 was high in peripheral blood of the same group. Expression of TNF and IFNγ in peripheral blood of the PM + group was high. Similarly, the apoptotic index and Fas expression were significantly high in PM+. However, FasL expression was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and hypoxia markers (COX-1, COX-2) were high in the PM + group. CONCLUSION: During placental malaria expression of some pro-inflammatory cytokines is up-regulated and markers of hypoxia and tissue damage are increased in cases of submicroscopic infection.

Severe Plasmodium vivax malaria, Brazilian Amazon.

We describe a case series of 17 patients hospitalized in Manaus (western Brazilian Amazon) with PCR-confirmed Plasmodium vivax infection who were treated with chloroquine and primaquine. The major complications were jaundice and severe anemia. No in vivo chloroquine resistance was detected. These data help characterize the clinical profile of severe P. vivax malaria in Latin America.

Endemias e epidemias na Amazônia: malária e doenças emergentes em áreas ribeirinhas do Rio Madeira: um caso de escola / Endemics and epidemics in the Amazon

Após fazer uma análise da evolução da malária na Amazônia brasileira, detalhando em particular a situação em Rondônia e no município de Porto Velho, onde ocorreram episódios dramáticos de epidemias de malária no passado, os autores apresentam o quadro atual da prevalência de malária nas áreas do Vale do Rio Madeira, que sofrerão impactos com a construção das hidrelétricas de Santo Antônio e Jirau, e alertam sobre a situação particular da malária em áreas ribeirinhas. Nessas áreas, observam-se alta incidência de malária vivax e falciparum, a presença de grande número de portadores assintomáticos de parasitas e altas densidades do vetor Anopheles darlingi o ano todo. Esses elementos, associados à provável chegada de migrantes oriundos de áreas não-endêmicas de Rondônia e de outros Estados do país, atraídos pela possibilidade de trabalho nessas hidrelétricas e oportunidades de comércio, lazer, educação e atividades domésticas, criam condições favoráveis à ocorrência de epidemias de malária e de outras doenças tropicais se não forem realizadas intervenções adequadas de controle, em particular no domínio do saneamento.

Molecular epidemiology of Plasmodium vivax in the State of Amazonas, Brazil.

Over the past 2 decades, the Amazon region of Brazil has experienced reemergence of Plasmodium vivax malaria, with reported occurrence of severe disease. The frequency and manifestations of this severe disease are unlike previous clinical experience. The hypothesis has been raised that the occurrence of severe disease may relate to the emergence of a variant form of the parasite. To test this hypothesis, we conducted a retrospective cohort study of P. vivax strains in the State of Amazonas. We determined nucleic acid sequences of segments of three genes, the 18S SSUrRNA Type A gene, the circumsporozoite surface protein (CSP) gene and the MSP-1 gene. Sequences were determined for parasites infecting 11 hospitalized (Inpatients) and 21 non-hospitalized (Outpatients) patients. We observed two common polymorphisms in the 18S SSUrRNA Type A gene; a thymidine (T)/adenine (A) polymorphism at residue 117 was significantly more common in the Inpatient group (p<0.05). Types of variation in the CSP gene included the numbers of repeat nonapeptide segments, alanine/aspartic acid polymorphism at position 5 of the nonapeptide repeat, and sporadic mutations. Alanine was more common as the fifth residue of the nonapeptide repeat in Inpatients and in strains causing second infections (both, p<0.05). Synonymous substitutions of the common repeat sequence occurred frequently in codons 1, 2, and 7, while the mutations at codon 5 were always non-synonymous, indicating that variation at codon 5 reflected selective pressure. Among MSP-1 gene sequences, recombination among progenitor strains, related to the Salvador I and Belém strains, was the main source of diversity. Phylogenetic analyses that incorporated sequence data for all three genes tested did not reveal clustering of sequences from inpatients. Our data do not affirm that the hypothesis that severe P. vivax disease in Amazonas is related to emergence of a new variant, but do suggest that variation in the fifth position of the CSP gene nonapeptide repeat may relate to disease manifestations.

Aotus lemurinus griseimembra monkeys: a suitable model for Plasmodium vivax sporozoite infection.

This study describes a successful Plasmodium vivax sporozoite infection in Aotus lemurinus griseimembra. Twenty-eight naive or previously infected monkeys, either splenectomized or spleen intact, were inoculated intravenously or subcutaneously with Plasmodium vivax sporozoites of the Salvador I strain or with two wild isolates (VCC-4 and VCC-5; Vivax-Cali-Colombia). The monkeys were successfully infected regardless of the parasite strain, spleen presence, or inoculation route and showed prepatent periods that ranged from 16 to 89 days. Only one monkey inoculated intravenously failed to develop parasitemia. Since immune protection against malaria pre-erythrocytic forms is mediated by both helper and cytolytic T cells that may home in the spleen and P. vivax cultures are not yet available; the use of spleen-intact A. lemurinus griseimembra, susceptible to both adapted and non-adapted strains of P. vivax sporozoites, is a valuable model for evaluation of pre-erythrocytic vaccine candidates.

Hemoglobin levels related to days of illness, race, and Plasmodium species in Colombian patients with uncomplicated malaria.

Prevalence of malaria-related anemia in disease-endemic regions of the American continents has been poorly studied. We describe the relationships between hemoglobin level and race, Plasmodium species, and days of illness in 150 Colombian patients with uncomplicated malaria diagnosed by thick blood smear. Hemoglobin was measured at admission and a standardized questionnaire was used to determine days of illness and other variables. Associations between hemoglobin and the variables were estimated and adjusted according to the other covariates using regression analysis. Plasmodium falciparum and P. vivax were found in similar proportions and mild anemia was present in 50% of the patients. Volunteers were classified as Afro-Colombians (61%) and non-Afro-Colombians (39%). An inverse relationship between hemoglobin and days of illness was identified, and a statistical interaction was found between race and P. falciparum infection in determining the hemoglobin concentration. These observations could guide the design of research to better understand malarial anemia.

The reproductive endocrine response to Plasmodium vivax infection in Hondurans.

Reproductive physiology and endocrinology change with the onset of illness and injury in a variety of species, including humans. To assess the human reproductive endocrine response to malaria, serial serum samples were collected from 8 male and 9 female residents of Honduras infected with Plasmodium vivax (plus 19 male and 23 female healthy age-matched controls) and were analyzed for associations between testosterone, parasitemia, and cytokine levels. Because testosterone has been negatively associated with measures of immune function under various circumstances, it was hypothesized that testosterone would be directly associated with P. vivax parasitemia and inversely associated with proinflammatory cytokine levels. The findings presented here suggest that 1) testosterone levels are positively associated with P. vivax parasitemia in adult males, and 2) males infected with P. vivax exhibit significantly lower testosterone levels and significantly higher cortisol levels than healthy individuals. Depressed androgen levels during physiologic perturbations may be an advantageous, adaptive host response to ameliorate immunosuppression by higher testosterone levels and to curb the use of energetic resources for metabolically expensive anabolic functions.

HLA class II and antibody responses to circumsporozoite protein repeats of P. vivax (VK210, VK247 and P. vivax-like) in individuals naturally exposed to malaria.

We studied the seroreactivity against the circumsporozoite protein (CSP) repeats of Plasmodium vivax variants in individuals living in malaria-endemic area of the Brazilian Amazon region (Candeias do Jamari - RO). The prevalence of IgG antibodies for at least one of the P. vivax CSP repeats was 49%. Among these positive individuals, 34.2% were positive for the standard repeat sequence VK210, 24% for the VK247 and 31.5% for the P. vivax-like sequence. HLA typing showed an association between antibody responses to the CS repeats of VK247 and the presence of HLA-DR16 and between HLA-DR7 and the absence of antibody responses to the CS repeats of VK210. We also investigated the potential relationship between HLA-DQB1 allele profile and antibody response to the CSP repeats of P. vivax but no segregation with responding profile was evidenced. The observed findings indicate that antibody responses to the CSP repeats of P. vivax variants appear to be modulated by HLA class II molecules in malaria naturally exposed individuals.

Malaria por Plasmodium vivax: aspectos clínicos y hematológicos / Malaria due to Plasmodium vivax. Clinical and hematological aspects

Se reportan los hallazgos clínicos, de laboratorio e histopatológicos, presentes en 20 pacientes que ingresaron al Hospital Hipólito Unanue en el año 1984, con el diagnóstico de malaria. Se revisa la fisiopatología con énfasis en los casos de malaria por Plasmodium vivax. El agente etiológico más frecuente, en esta serie, fue el Plasmodium vivax ( 19 pacientes ). Fiebre y escalofrío se presentó en el 100 por ciento, hepatomegalia en el 90 por ciento, esplenomegalia en el 70 por ciento, ictericia en el 30 por ciento, esta última fue muy severa en un caso asociada a hepatitis crónica activa. La anemia que se observó en el 85 por ciento, fue de origen multifactorial; la trombocitopenia estuvo presente en el 83.3 por ciento de casos, rara vez se acompañó de sangrado. Otros hallazgos fueron: linfopenia ( 70 por ciento ), leucopenia leve ( 45 por ciento ), neutropenia leve ( 35 por ciento ). La histopatología en médula ósea mostró: hiperplasia de las tres series y cambios reactivos inespecíficos. En hígado encontramos: depósito de pigmento malárico en el 42.8 por ciento de casos. Dada las actuales condiciones sanitarias y epidemiológicas del país, es impostergable reforzar la lucha contra esta enfermedad

[Changes in gastric mucosa in acute malaria]. / Alteraciones de la mucosa gástrica en malaria aguda.

A high incidence rate of Malaria is observed at Bolívar state (Venezuela) and, beside classic acute symptomatology, we have observed gastric symptoms like epigastralgia, anorexia, nausea and vomits. The scope of this study is to establish changes of gastric mucosa related to Plasmodium infection, using macro and microscopic technics. One hundred both sex patients with Malaria diagnosis done with thick drop technic and gastric symptomatology were studied in our department from March 1990 to February 1991. The esophagus, stomach and duodenum of all patients were evaluated with upper digestive tract endoscopy and still photographs, and biopsies of fundus, body and antrum were taken, fixed in 10% formaldehyde and stained with hematoxylin-eosine method. P. falciparum was found in 52 cases, P. vivax in 39 and 9 infected with both, most of patients complained of shivering fever, epigastralgia (76%), nausea and vomits (72%), tartness (25%) and burning pain (21%). Mucosal edema and congestion (gastritis) were the endoscopic findings in 88% of cases, usually located at antrum (67%) and fundus (33%). The microscopic findings were: mucosal edema (90%), superficial bleeding (87%), microthrombosis (60%), gastric atrophy (40%) and intestinal metaplasia (8%). Acute gastric symptomatology we have observed in patients with acute malaria my be due to microthrombosis and arteriolar occlusion, leading to ischemic changes and mucosal edema. These pathophysiological changes explain most of upper digestive tract symptoms in acute malaria, particularly when agent is P. falciparum. We have not found related papers in bibliography.

The role of cytokines in Plasmodium vivax malaria.

The cytokine tumor necrosis factor and other as yet unidentified factor(s) which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s) are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TNF levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheless serum TNF levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.