Plasmodium Vivax Malaria Patients Research Articles

Risk of hemolysis in Plasmodium vivax malaria patients receiving standard primaquine treatment in a population with high prevalence of G6PD deficiency.

Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity. In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28days after treatment with the standard chloroquine and 14-day primaquine (0.25mg/kg/day) regimen. Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion. The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.

Liver and kidney dysfunction, hypoglycemia, and thrombocytopenia in Plasmodium vivax malaria patients at a Colombian Northwest region

Plasmodium vivax has high morbidity, it is the Plasmodium species with the greatest worldwide distribution, and its ability to trigger severe symptoms is currently recognized. The present study aims to compare the clinical and epidemiological characteristics of patients with P. vivax malaria, with and without complication criteria, in an endemic area for malaria transmission in northwest Colombia. A descriptive cross-sectional study was carried out between 2017 and 2019, patients with P.vivax severe malaria (n = 50), non-severe malaria (n = 56) and healthy controls (n = 50) were included. Sociodemographic, clinical, hematological, and biochemical characteristics were analyzed. Clinical follow-up was carried out in a group of patients with severe malaria. The statistical analysis was carried out in GraphPad Prism; the Chi-square test analyzed categorical variables, comparisons of variables for the three groups were carried out by the Kruskal-Wallis test and comparison between two groups by the Mann-Whitney test. A multiple correspondence analysis described the relationship between variables, which was carried out through the R software. One hundred fifty-six individuals were linked to the study, 76 women and 80 men, between 3 and 71 years old. For 50% of the patients, it was their first malaria episode; 42% of the patients classified with severe malaria required hospitalization, compared to 7.1% of the patients with non-severe malaria. Parasitaemia was similar in both clinical groups; however, 10% of severe patients presented high parasitemia, between 20,000-135,000. The most frequent clinical characteristics in patients with severe malaria were severe thrombocytopenia in 54%, hypoglycemia in 48%, and liver and kidney failure in 30%. Biochemical and hematological parameters returned to normal in 90% of the patients with severe malaria on the third day after starting treatment. Thrombocytopenia, hypoglycemia, and liver and kidney dysfunctions were the most frequent P. vivax malaria complications in this study. Hemoglobin concentration and parasite count were not related to the clinical condition of patients. Thrombocytopenia was the most frequent finding in patients with malaria, and its severity presented an inverse relationship with the number of previous malaria episodes.

Platelet Alteration in Plasmodium vivax Malaria Patients in Thailand

Introduction: Malaria remains a global health problem. Malaria is often linked to thrombocytopenia as well as other hematological variations.
 Objective: The aim of this study is to find the platelet changes in Plasmodium vivax malaria patients. This retrospective cross-sectional study included 204 malaria patients admitted to the Hospital for Tropical Diseases, Bangkok, Thailand.
 Results: Thrombocytopenia (<150x103/µl) was seen in 170(83.3%) patients with a mean (SD) of 101x103/µl (56.5). Mild (150x103/µl-50x103/µl), moderate (50x103/µl-20x103/µl) and severe (<20x103/µl) thrombocytopenia were seen in 141 (69.1%), 25 (12.2%) and 4 (2%) patients respectively. None of these patients with thrombocytopenia showed any sign of bleeding or required platelet transfusion.
 Conclusion: This study showed thrombocytopenia as a classic feature of vivax malaria presenting more than 80% of cases. In patients with profoundly low thrombocyte counts there was no manifestation of bleeding nor was any platelet transfusion required.

CYP2D6 activity and the risk of recurrence of Plasmodium vivax malaria in the Brazilian Amazon: a prospective cohort study

BackgroundCYP2D6 pathway mediates the activation of primaquine into active metabolite(s) in hepatocytes. CYP2D6 is highly polymorphic, encoding CYP2D6 isoforms with normal, reduced, null or increased activity. It is hypothesized that Plasmodium vivax malaria patients with defective CYP2D6 function would be at increased risk for primaquine failure to prevent recurrence. The aim of this study was to investigate the association of CYP2D6 polymorphisms and inferred CYP2D6 phenotypes with malaria recurrence in patients from the Western Brazilian Amazon, following chloroquine/primaquine combined therapy.MethodsThe prospective cohort consisted of P. vivax malaria patients who were followed for 6 months after completion of the chloroquine/primaquine therapy. Recurrence was defined as one or more malaria episodes, 28–180 days after the initial episode. Genotyping for nine CYP2D6 SNPs and copy number variation was performed using TaqMan assays in a Fast 7500 Real-Time System. CYP2D6 star alleles (haplotypes), diplotypes and CYP2D6 phenotypes were inferred, and the activity score system was used to define the functionality of the CYP2D6 diplotypes. CYP2D6 activity scores (AS) were dichotomized at ≤ 1 (gPM, gIM and gNM-S phenotypes) and ≥ 1.5 (gNM-F and gUM phenotypes).ResultsGenotyping was successfully performed in 190 patients (44 with recurrence and 146 without recurrences). Recurrence incidence was higher in individuals presenting reduced activity CYP2D6 phenotypes (adjusted relative risk = 1.89, 95% CI 1.01–3.70; p = 0.049). Attributable risk and population attributable fraction were 11.5 and 9.9%, respectively. The time elapsed from the first P. vivax malaria episode until the recurrence did not differ between patients with AS of ≤ 1 versus ≥ 1.5 (p = 0.917).ConclusionsThe results suggest that CYP2D6 polymorphisms are associated with increased risk of recurrence of vivax malaria, following chloroquine–primaquine combined therapy. This association is interpreted as the result of reduced conversion of primaquine into its active metabolites in patients with reduced CYP2D6 enzymatic activity.

Pengaruh suplementasi seng dan vitamin B6 terhadap kadar hemoglobin, hematokrit dan indeks eritrosit pasien malaria vivax yang anemia

Background: Zinc supplementation decrease the risk of malaria parasitaemia, increasing ferritin serum level and hemoglobin in patients with malaria. Zinc influence the activity of aminolevulinic acid dehydratase (ALAD) an enzymes that catalizes heme synthesize. Vitamin B6 in pyridoxal 5-phosphate (PLP) from has a role in alpha-aminolevulinic acid (ALA) formation, which is the precursor of heme in hemoglobin. PLP also inhibit the growth of the malaria parasite.Objective: The objective was to analyze the effect of zinc and vitamin B6 supplementation on hemoglobin level, hematocrit and erythrocyte indexs (MCV, MCH and MCHC) of anemic Plasmodium vivax malaria patients.Methods: Double Blind Randomised Controlled Trial with pre and post test design. 30 subjects were divided into two groups: the suplementation group were given zinc 1x10 mg/day with vitamin B6 1x5 mg/day and the control group were given a placebo for 30 days. Data analysis by paired t-test, independent t-test and Mann Whitney.Results: There was an increase in Hb levels in the suplementation group (p=0.0001), the control group (p=0.001) and there was a significant difference on the increase between the two groups (p=0.020). Hematocrit significant increase only in the suplementation group (p=0.0001). There were no differences on erythrocyte index parameter in both groups.Conclusion: Zinc and vitamin B6 supplementation of for 30 days increase the hemoglobin level, hematocrit and there were no effect on erythrocyte indexs of anemic Plasmodium vivax malaria patients.

Surmised total leucocyte counts miscalculate the parasite index of Plasmodium vivax malaria patients of tertiary and primary care settings in South-Western India

BackgroundFor the calculation of parasite index (PI) by microscopy method, an assumed total leucocyte count (TLC) of 8,000/μL is used conventionally. However, due to obvious variation in the population and individual TLCs, use of 8,000/μL may result in either over/underestimation of the PI.MethodsThis study was aimed at ascertaining the utility of 8,000/μL TLC, as well as other assumed TLCs, with respect to measured TLC for the calculation of PI. A tertiary care hospital and five primary health centres were the base for the prospective study conducted among microscopically proven, symptomatic Plasmodium vivax mono-infection patients aged ≥18 years. PIs calculated by assumed TLCs ranging from 4,000-11,000/μL were compared with those calculated by measured TLCs. Geometric mean with 95% confidence interval, Bland-Altman plot and Wilcoxon signed rank test were used for statistical analysis.ResultsA total of 284 P. vivax mono-infection patients, including 156 from a tertiary care hospital and 128 from five primary health centres, were recruited in the study. Assumed TLCs below 5,000 cell/μL and above 5,500 cell/μL in tertiary care setting resulted in significant (p <0.05) underestimation and overestimation, respectively. However, in primary health centres, it was an assumed TLC of 5,000 cell/μL, below and above which there was significant (p <0.05) underestimation and overestimation observed, respectively.ConclusionsAssumed TLC of 8,000/μL is not suitable for the calculation of PI. Either actual TLC of the patient should be measured or a representative TLC should be derived for the population under investigation for any study requiring calculated PI by microscopy.

The frequency of HLA-DRB1 polymorphisms in Brazilian Plasmodium vivax malaria patients and in blood donors from the Amazon Region

We evaluated the frequency of different HLA-DRB1 alleles in Plasmodium vivax-infected individuals and in healthy blood donors from malaria endemic areas of Brazil. Low-resolution human leukocyte antigen-DRB1 genotyping was performed for 73 malaria patients and 29 healthy blood donors. The most frequent alleles in individuals from northern Brazil were human leukocyte antigen-DRB1*04, *08, *07 and *13. The frequency of human leukocyte antigen-DRB1*07 was higher in malaria-infected individuals than in the control group, which reinforces the theory that this allele plays an important role in susceptibility to malaria. This study offers new information about a potential susceptibility factor for P. vivax malaria in a Brazilian population that is naturally exposed to malaria.

A preliminary study on pro- and anti-inflammatory cytokine profiles in Plasmodium vivax malaria patients from central zone of India

The aim of this preliminary study was to investigate the plasma cytokine profiles in a group of patients suffering from Plasmodium vivax malaria during the peak of its transmission season. Plasma samples of 173 P. vivax patients and 34 healthy individuals were analyzed for IFN-gamma, TNF-alpha, IL-10 and IP-10 levels by ELISA. Levels of both pro- and anti-inflammatory cytokines were significantly higher in P. vivax patients compared to controls. Children with P. vivax infection had significantly higher levels of IFN-gamma than adults (P=0.017). Asexual parasitaemia versus TNF-alpha (r=-0.31, P=0.01), IL-10 (r=-0.30, P=0.015) and gametocytaemia versus IFN-gamma (r=-0.26; P=0.034) levels showed significant negative correlation in children compared to adults. The median concentrations of IFN-gamma (P=0.001), IL-10 (P=0.032) and IP-10 (P</=0.05) were higher in children reported with chills and rigors, whereas in adults only IFN-gamma levels was higher (P<0.0001). The median plasma concentrations of IFN- gamma (P=0.02), IL-10 (P<0.0001) and IP-10 (P=0.068) were higher in patients with mild anaemia compared to non-anaemic patients. The results indicated that both pro- and anti-inflammatory cytokine responses are associated with clinical signs of mild anaemia and paroxysm during symptomatic P. vivax malaria in Central India.

Methemoglobinemia and Adverse Events in Plasmodium vivax Malaria Patients Associated with High Doses of Primaquine Treatment

Primaquine (PQ) is recommended to prevent relapses in patients with Plasmodium vivax malaria infection. However, treatment with PQ causes methemoglobinemia. In this study, we measured the methemoglobin (MetHB) levels in three groups of subjects who received PQ treatment at 0.58, 0.83, or 1.17 mg/kg/d. A total of 112 subjects were studied. MetHB levels were detected at > or = 4% in 46-50% 1 day after PQ treatment in all three groups and 4-9% of subjects had MetHB levels > or = 4% 15 days after treatment. Only subjects receiving the highest doses of PQ had mild and brief adverse events, and 17% of them were associated with treatment. We conclude that when PQ is administered under certain conditions (i.e., normal glucose-6-phosphate dehydrogenase activity, in non-pregnant subjects and with a light meal), daily doses as high as 1.17 mg/kg do not represent a serious risk of high MetHB levels to patients.

Chloroquine-resistant Plasmodium vivax in the Republic of Korea

The number of Plasmodium vivax malaria patients in the Republic of Korea and North Korea since the re-emergence of malaria in 1993 is estimated to be approximately one million. To cope with this situation, the Army of the Republic of Korea has performed chemoprophylaxis with hydroxychloroquine and primaquine since 1997. The cumulative number of soldiers in the Army of the Republic of Korea given chemoprophylaxis exceeded 1.4 million by 2007. Extensive chemoprophylaxis contributed to preventing a rapid increase of malaria patients in the Army of the Republic of Korea, but increased the possibility of the occurrence of chloroquine (CQ)-resistant P. vivax strains. In this study, treatment responses of P. vivax malaria patients in the Republic of Korea monitored during 2003-2007, and CQ resistance was confirmed in 2 of 484 enrolled patients. Our results are the first report of CQ-resistant P. vivax in a temperate region of Asia. Continuous surveillance is warranted to monitor the change in CQ resistance frequency of P. vivax in the Republic of Korea.

Tumour necrosis factor-dependent parasite-killing effects during paroxysms in non-immune Plasmodium vivax malaria patients.

Plasmodium vivax malaria infections in non-immune individuals manifest as periodic clinical episodes of fever with chills and rigors known as paroxysms. We have demonstrated that in non-immune patients the period of paroxysm is associated with the transient presence of plasma factors which kill gametocytes, the intra-erythrocytic sexual stages of the malaria parasite which transmit the infection from humans to mosquito, rendering them non-infectious to mosquitoes. Gametocyte killing in paroxysm plasma is mediated by tumour necrosis factor (TNF) acting in conjunction with other essential serum factor(s). Plasma TNF levels were elevated during a paroxysm. In semi-immune individuals from a P. vivax-endemic area clinical symptoms of malaria are mild and the parasite killing factors are not induced during paroxysm. Serum TNF levels were correspondingly lower in endemic patients during a paroxysm. Human peripheral blood mononuclear cells (PBMC) can be stimulated in vitro by extracts of P. vivax blood stage parasites to produce TNF and associated parasite killing factor(s), thus simulating in vitro the events that occur during a paroxysm, this being the release of parasite exo-antigens by rupturing schizonts and the subsequent induction of PBMC to produce TNF and other parasite-killing factors. We were able to show that convalescent serum from P. vivax semi-immune individuals block the induction of TNF and parasite-killing factors by malaria antigens in vitro, presumably through antibodies that neutralize parasite exo-antigens. Thus, individuals living in malaria-endemic areas appear to acquire clinical immunity to malaria by avoiding their induction during infection; we have shown that one such mechanism is the neutralization of parasite exo-antigens that induce the production of parasite killing factors.

Serum cytokine profiles in patients with Plasmodium vivax malaria: A comparison between those who presented with and without hepatic dysfunction

The aim of this study was to compare the serum cytokine profiles of Plasmodium vivax malaria patients who presented with and without hepatic dysfunction. This is a retrospective analysis of 74 consecutive cases of P. vivax malaria seen at 3 military hospitals near the Demilitarized Zone in South Korea from 1999 to 2000. All patients studied were adult active duty servicemen. On admission, the mean (± SEM) age of the patients who presented with ( n = 36) and without hepatic dysfunction ( n = 38) was 21.6 ± 0.24 and 22.5 ± 0.44 years, respectively ( P = 0.72). On admission, there was no significant difference between the 2 patient populations in terms of mean temperature, haemoglobin level, haematocrit, total white blood cell count, platelet count, parasite index, and serum concentration of transforming growth factor-β. Plasmodium vivax malaria patients who presented with hepatic dysfunction had significantly higher mean serum concentrations of soluble Fas ligand, interleukin (IL)-l, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ than those without hepatic dysfunction, suggesting the involvement of these cytokines in the development of hepatic dysfunction. The mean serum concentration of IL-12 was significantly lower in patients with hepatic dysfunction. The mean body temperature was not significantly different between the 2 patient populations.

Frequency of Pruritus inPlasmodium VivaxMalaria Patients Treated with Chloroquine in Thailand

Chloroquine-induced itch in black-skinned African malaria patients is common and frequently leads to poor compliance or treatment defaulting.To assess the frequency and severity of chloroquine-induced pruritus in an Asian population, we reviewed case records of 1189 Plasmodium vivax malaria patients treated with chloroquine (25 mg/kg over 3 days) at the Bangkok Hospital for Tropical Diseases from 1992 through 1997. The majority of patients were Thais or ethnic Burmese (light brown skin), referred from the western border of Thailand. Overall, there were 23 patients (1.9%) with complaints of pruritus during chloroquine therapy. Of these, 12 (52%) had palm and sole involvement, eight (35%) had generalized pruritus including the palms and soles, and three (13%) had palm itching only. One patient developed pruritus on the palms and soles on two consecutive admissions. The pruritus did not interfere with daily activity, was reduced in intensity by anti-histamine therapy, and did not affect the patient's willingness to complete the chloroquine regimen. Therapeutic responses in the 23 patients with chloroquine itch was similar to those without itch. Among the itch patients, there was no association with gender or level of parasitaemias. Our findings indicate that the frequency of chloroquine-induced pruritus in Asian patients treated with chloroquine for P. vivax malaria is low in comparison with black-skinned Africans.This may be related to pharmacogenetic factors, the infective Plasmodium species, drug metabolism or drug-parasite interactions, or a lower affinity of chloroquine for less pigmented skin.

Demonstration of anti-disease immunity to Plasmodium vivax malaria in Sri Lanka using a quantitative method to assess clinical disease.

Clinical immunity to malaria was studied by quantifying the intensity of symptoms as well as by measurement of several hematologic indicators of pathology (the erythrocyte sedimentation rate [ESR], serum bilirubin, reticulocyte count, plasma tumor necrosis factor-alpha [TNF-alpha], and blood glucose levels) in 39 Plasmodium vivax malaria patients exposed to endemic malaria in southern Sri Lanka, and for comparison in 43 nonimmune patients who were residents of nonmalarious regions of the country. The intensity of 11 symptoms was scored numerically in all patients using a questionnaire. This clinical score was validated by introducing internal controls to the questionnaire, and by correlating it with the underlying pathology. Both the intensity of clinical disease as well as the degree of underlying pathology were found to be significantly lower in endemic area patients (mean clinical score = 8.8, median ESR = 8 mm) compared with the nonendemic area patients (mean clinical score = 19.0, median ESR 31.5 mm). Endemic area patients also had lower parasite densities (mean = 0.06%) than those from the nonendemic area (0.12%) (P < 0.05). However, at any parasite density, both clinical disease and pathology were significantly less in the endemic area patients (P < 0.001, for both clinical score and ESR), indicating that the clinical immunity seen in the endemic area patients was a true tolerance of parasites. Although plasma TNF-alpha levels were elevated in both groups of patients, they were significantly higher in the nonendemic area patients than in patients from the endemic area (P < 0.01). Furthermore, at comparable levels of plasma TNF-alpha, nonendemic area patients had both a higher intensity of clinical disease and an underlying pathology than those from the endemic area, suggesting that if TNF-alpha is indeed a mediator of clinical disease, the endemic area patients may be tolerant to its effects. Hypoglycemia was not observed in any of these P. vivax patients despite some with high levels of plasma TNF-alpha.

Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p < 0.005 and < 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted < or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p < 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.