Malaria Research and Treatment最新文献

This study investigated potential risk factors associated with malaria transmission in Tubu village, Okavango subdistrict, a malaria endemic area in northern Botswana. Data was derived from a census questionnaire survey, participatory rural appraisal workshop, field observations, and mosquito surveys. History of malaria episodes was associated with several factors: household income (P < 0.05), late outdoor activities (OR = 7.016; CI = 1.786-27.559), time spent outdoors (P = 0.051), travel outside study area (OR = 2.70; CI = 1.004-7.260), nonpossession of insecticide treated nets (OR = 0.892; CI = 0.797-0.998), hut/house structure (OR = 11.781; CI = 3.868-35.885), and homestead location from water bodies (P < 0.05). No associations were established between history of malaria episodes and the following factors: being a farmer (P > 0.05) and number of nets possessed (P > 0.05). Eave size was not associated with mosquito bites (P > 0.05), frequency of mosquito bites (P > 0.05), and time of mosquito bites (P > 0.05). Possession of nets was very high (94.7%). Close proximity of a health facility and low vegetation cover were added advantages. Some of the identified risk factors are important for developing effective control and elimination strategies involving the community, with limited resources.

Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T 1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85 ± 1.94 h, 13.77 ± 2.05 h, and 878.74 ± 133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

Background. While research on P. vivax is scarce because it is considered benign, it has become evident with implementation of molecular diagnosis that it can also cause multiple organ dysfunction and severe life-threatening disease. Objective. To study clinical presentations and complications of P. vivax malaria and mortality correlation to severity parameters as defined by WHO criteria for severe malaria. Materials and methods. This study was conducted in a tertiary care centre in Mumbai. Confirmed P. vivax cases were enrolled and studied for their clinical profile, and WHO severity parameters were tested for their frequency and association to mortality. Result. The most common presentation was fever followed by pallor. 26% of the cases satisfied one or more criteria of WHO severity parameters. 2 cases died; both had pulmonary edema and bleeding. The major predictor of mortality among these predefined severity criteria was pulmonary edema/ARDS. Patients with severe anemia, circulatory collapse, and repeated generalized convulsion had 100% survival rate. Leukopenia was present in 10% of the cases. Both cases with mortality had leukopenia. Conclusion. P. vivax monoinfection tends to have severe complications in children. There is a need to review severity criteria for P. vivax malaria.

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a valuable vaccine candidate and exported on the merozoite surface at the time of erythrocyte invasion. PfAMA1 interacts with rhoptry neck protein PfRON2, a component of the rhoptry protein complex, which forms the tight junction at the time of invasion. Phage display studies have identified a 15-residue (F1) and a 20-residue (R1) peptide that bind to PfAMA1 and block the invasion of erythrocytes. Cocrystal structures of central region of PfAMA1 containing disulfide-linked clusters (domains I and II) with R1 peptide and a peptide derived from PfRON2 showed strong structural similarity in binding. The peptides bound to a hydrophobic groove surrounded by domain I and II loops. In this study, peptidomimetics based on the crucial PfAMA1-binding residues of PfRON2 peptide have been identified. Top 5 peptidomimetics when checked for their docking on the region of PfAMA1 encompassing the hydrophobic groove were found to dock on the groove. Drug-like molecules having structural similarity to the top 5 peptidomimetics were identified based on their binding ability to PfAMA1 hydrophobic groove in blind docking. These inhibitors provide potential lead compounds, which could be used in the development of antimalarials targeting PfAMA1.

Background. Efficacy of standard dose of primaquine (PQ) as antirelapse for P. vivax has decreased. We aimed to assess efficacy of different PQ regimens. Methods. It was an open label, randomized, controlled, parallel group, assessor blind study comparing antirelapse efficacy of 3 PQ regimens (B = 15 mg/day × 14 days, C = 30 mg/day × 7 days, and D = 30 mg/day × 14 days) with no PQ group (A) in P. vivax patients. Paired primary and recurrence samples were subjected to 3 methods: (i) month of recurrence and genotyping, (ii) by PCR-RFLP, and (iii) PCR sequencing, to differentiate relapse and reinfection. The rates of recurrence relapse and reinfection were compared. Methods were compared for concordance between them. Results. The recurrence rate was 16.39%, 8.07%, 10.07%, and 6.62% in groups A, B, C, and D, respectively (P = 0.004). The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% (P = 0.007) as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting.

Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs) on an antimalarial candidate 99/411 pharmacokinetic (PK) profile. Method. For this, single oral dose PK drug interaction studies were conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT), Carbamazepine (CBZ), and Gabapentin (GB) in both male and female SD rats, to assess the coadministered and intersexual influences on 99/411 PK profile. Results. Studies revealed that there were no significant alterations in the PK profile of 99/411 upon PHT and CBZ coadministration in both male and female rats, while systemic exposure of 99/411 was significantly increased by about 80% in female rats upon GB coadministration. In terms of AUC, there was an increase from 2471 ± 586 to 4560 ± 1396 ng·h/mL. Overall, it was concluded that simultaneous administration of AEDs with 99/411 excludes the requirements for dose adjustment, additional therapeutic monitoring, contraindication to concomitant use, and/or other measures to mitigate risk, except for GB coadministration in females. These findings are further helpful to predict such interactions in humans, when potentially applied through proper allometric scaling to extrapolate the data.

Background. Malaria is a one of the leading causes of morbidity and mortality in tropical countries. Plasmodium vivax (P. vivax) is usually thought to be causing benign malaria with low incidence of complications as compared to Plasmodium falciparum (P. falciparum). Methods. This retrospective observational study included malaria patients who were admitted to K.T. Children Hospital and P.D.U. Government Medical College, Rajkot, a tertiary care teaching hospital, Gujarat, western India, during the period January 2012 to December 2012. Inclusion criteria were patients in whom either P. falciparum or P. vivax was positive on rapid malaria antigen test and peripheral blood smear. Patients showing mixed infections were excluded from study. Results. A total of 79 subjects (mean age 5.4 ± 3.6 years) were included in the study. It consisted of 47 P. vivax and 32 P. falciparum cases. The P. vivax cases consisted of 33 (70.2%) males and 11 (19.8%) females while P. falciparum cases consisted of 14 (43.8%) males and 18 (56.2%) females. One patient of each P. vivax and P. falciparum expired. There was no statistical significant difference found between complications such as anemia, thrombocytopenia, liver and renal dysfunction, ARDS, and cerebral malaria between P. vivax and P. falciparum. Conclusion. We conclude that P. vivax monoinfection tends to have as similar course and complications as compared to malaria due to P. falciparum monoinfection.

Background. Malaria's prevalence during pregnancy varies widely in parts of sub-Saharan Africa, including Burkina Faso. The objective of this study was to evaluate the incidence of mother-to-child malaria transmission during childbirth at St. Camille Medical Centre in the city of Ouagadougou. Methods. Two hundred and thirty-eight (238) women and their newborns were included in the study. Women consenting to participate in this study responded to a questionnaire that identified their demographic characteristics. Asymptomatic malaria infection was assessed by rapid detection test Acon (Acon Malaria Pf, San Diego, USA) and by microscopic examination of Giemsa-stained thick and thin smears from peripheral, placental, and umbilical cord blood. Birth weights were recorded and the biological analyses of mothers and newborns' blood were also performed. Results. The utilization of long-lasting insecticidal nets (LLINs) and intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) were 86.6% and 84.4%, respectively. The parasitic infection rates of 9.5%, 8.9%, and 2.8% were recorded, respectively, for the peripheral, placental, and umbilical cord blood. Placental infection was strongly associated with the presence of parasites in the maternal peripheral blood and a parasite density of >1000 parasites/µL. Conclusion. The prevalence of congenital malaria was reduced but was associated with a high rate of mother-to-child malaria transmission.

Background. Although eradicated in Portugal, malaria keeps taking its toll on travelers and migrants from endemic countries. Disease notification is mandatory but is compromised by underreporting. Methods. A retrospective study on malaria hospitalizations for 10 consecutive years (2000-2009) was conducted. Data on hospitalizations and notifications were obtained from Central Administration of Health System and Health Protection Agency, respectively. For data selection ICD-9 CM and ICD-10 were used: codes 084(*), 647.4, and B50-B54. Variables were gender, age, agent and origin of infection, length of stay (LOS), lethality, and comorbidities. Analysis included description, hypothesis testing, and regression. Results. There were 2003 malaria hospitalizations and 480 notified hospitalized cases, mainly in young male adults. P. falciparum was the main agent of infection acquired mainly in sub-Saharan Africa. Lethality was 1.95% and mean LOS was 8.09 days. Older age entailed longer LOS and increased lethality. Discussion. From 2000 to 2009, there were 2003 malaria hospitalizations with decreasing annual incidence, these numbers being remarkably higher than those notified. The national database of diagnosis related groups, reflecting hospitalizations on NHS hospitals, may be an unexplored complementary source for better estimates on imported malaria.

Background. Malaria still remains a public health problem in developing countries and changing environmental and climatic factors pose the biggest challenge in fighting against the scourge of malaria. Therefore, the study was designed to forecast malaria cases using climatic factors as predictors in Delhi, India. Methods. The total number of monthly cases of malaria slide positives occurring from January 2006 to December 2013 was taken from the register maintained at the malaria clinic at Rural Health Training Centre (RHTC), Najafgarh, Delhi. Climatic data of monthly mean rainfall, relative humidity, and mean maximum temperature were taken from Regional Meteorological Centre, Delhi. Expert modeler of SPSS ver. 21 was used for analyzing the time series data. Results. Autoregressive integrated moving average, ARIMA (0,1,1) (0,1,0)(12), was the best fit model and it could explain 72.5% variability in the time series data. Rainfall (P value = 0.004) and relative humidity (P value = 0.001) were found to be significant predictors for malaria transmission in the study area. Seasonal adjusted factor (SAF) for malaria cases shows peak during the months of August and September. Conclusion. ARIMA models of time series analysis is a simple and reliable tool for producing reliable forecasts for malaria in Delhi, India.