Quantitative standardization of pharmacologically active components from antiplasmodial plant Solanum nudum Dunal (wild and in vitro)

Solanum nudum Dunal (Solanaceae) is most commonly known and used by the population of the colombian Pacific coast as an antimalarial treatment. This article study into optimization and quantitative analysis of compounds steroidal over time of development of this species when grown in vitro and wild. A new steroidal compound named SN6 was elucidated by NMR and a new method of quantification of seven steroidal compounds (Diosgenone DONA and six steroids SNs) using HPLC-DAD-MS in extracts of cultures in vitro and wild was investigated. Biology activity of extracts was found to a range of antiplasmodial activity in FCB2 and NF-54 with inhibitory concentration (IC50) between (17.04 -100 μg/mL) and cytotoxicity in U-937 of CC50 (7.18 -104.7 μg/mL). This method creates the basis for the detection of seven sterols antiplasmodial present in extracts from S. nudum plant as a quality parameter in the control and expression of phytochemicals.

Starting at the community: Treatment seeking pathways of children with suspected severe malaria in Uganda

IntroductionCommunity health workers (CHW) usually refer children with suspected severe malaria to the nearest public health facility or a designated public referral health facility (RHF). Caregivers do not always follow this recommendation. This study aimed at identifying post-referral treatment-seeking pathways that lead to appropriate antimalarial treatment for children less than five years with suspected severe malaria.MethodsAn observational study in Uganda enrolled children below five years presenting to CHWs with signs of severe malaria. Children were followed up 28 days after enrolment to assess their condition and treatment-seeking history, including referral advice and provision of antimalarial treatment from visited providers.ResultsOf 2211 children included in the analysis, 96% visited a second provider after attending a CHW. The majority of CHWs recommended caregivers to take their child to a designated RHF (65%); however, only 59% followed this recommendation. Many children were brought to a private clinic (33%), even though CHWs rarely recommended this type of provider (3%). Children who were brought to a private clinic were more likely to receive an injection than children brought to a RHF (78% vs 51%, p<0.001) and more likely to receive the second or third-line injectable antimalarial (artemether: 22% vs. 2%, p<0.001, quinine: 12% vs. 3%, p<0.001). Children who only went to non-RHF providers were less likely to receive an artemisinin-based combination therapy (ACT) than children who attended a RHF (odds ratio [OR] = 0.64, 95% CI 0.51–0.79, p<0.001). Children who did not go to any provider after seeing a CHW were the least likely to receive an ACT (OR = 0.21, 95% CI 0.14–0.34, p<0.001).ConclusionsHealth policies should recognise local treatment-seeking practices and ensure adequate quality of care at the various public and private sector providers where caregivers of children with suspected severe malaria actually seek care.

Prevalence and outcomes of malaria as co-infection among patients with human African trypanosomiasis: a systematic review and meta-analysis

Human African trypanosomiasis (HAT) is endemic in Africa; hence, the possibility of co-infection with malaria among patients with HAT exists. The present study investigated co-infection with malaria among patients with HAT to provide current evidence and characteristics to support further studies. Potentially relevant studies that reported Plasmodium spp. infection in patients with HAT was searched in PubMed, Web of Science, and Scopus. The risk of bias among the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. The pooled prevalence of Plasmodium spp. infection in patients with HAT was quantitatively synthesized using a random-effects model. Subgroup analyses of study sites and stages of HAT were performed to identify heterogeneity regarding prevalence among the included studies. The heterogeneity of the outcome among the included studies was assessed using Cochran’s Q and I2 statistics for consistency. Publication bias was assessed if the number of included studies was 10 or more. For qualitative synthesis, a narrative synthesis of the impact of Plasmodium spp. infection on the clinical and outcome characteristics of HAT was performed when the included studies provided qualitative data. Among 327 studies identified from three databases, nine studies were included in the systematic review and meta-analysis. The prevalence of Plasmodium spp. co-infection (692 cases) among patients with HAT (1523 cases) was 50% (95% confidence interval [CI] = 28–72%, I2 = 98.1%, seven studies). Subgroup analysis by type of HAT (gambiense or rhodesiense HAT) revealed that among patients with gambiense HAT, the pooled prevalence of Plasmodium spp. infection was 46% (95% CI = 14–78%, I2 = 96.62%, four studies), whereas that among patients with rhodesiense HAT was 44% (95% CI = 40–49%, I2 = 98.3%, three studies). Qualitative syntheses demonstrated that Plasmodium spp. infection in individuals with HAT might influence the risk of encephalopathy syndrome, drug toxicity, and significantly longer corrected QT time. Moreover, longer hospital stays and higher treatment costs were recorded among co-infected individuals. Because of the high prevalence of malaria among patients with HAT, some patients were positive for malaria parasites despite being asymptomatic. Therefore, it is suggested to test every patient with HAT for malaria before HAT treatment. If malaria is present, then antimalarial treatment is recommended before HAT treatment. Antimalarial treatment in patients with HAT might decrease the probability of poor clinical outcomes and case fatality in HAT.

Evidence of Plasmodium falciparum infection after 12 years from the exposure: cryptic malaria or recrudescence?

BackgroundMalaria infections affect a high percentage of the world's population, especially in tropical and subtropical regions. Specifically, Plasmodium falciparum is the most relevant species involved in the etiopathogenesis of this infection. The duration of P. falciparum infections is often undefined, as some reported episodes of suspected recrudescence occur several years after initial exposure.Case presentationWe present a case report of malaria infection with low parasitaemia in a man whose last stay in an endemic region or contacts with the local population was twelve years ago. The patient recovered fully with adequate antimalarial treatment, but some aspects of his clinical history were not clearly defined.ConclusionsWe discuss here the possibility that this is either a P. falciparum recrudescence or an episode of cryptic malaria, as we cannot carefully verify some details of our patient's life and history.

Pulmonary Complication in Severe Malaria

Malaria is a potentially fatal disease caused by Plasmodium spp. Transmission occurs via the bite of female mosquito, Anopheles spp. Epidemiologically, global number of malaria patient are located in Southeast Asia and Africa. Until nowadays, millions of people still living in endemic area, with children and pregnant women are among the most vulnerable group in the population. Although there have been many advances in treatment and management, but the potential for harm remains; one of the example is lung involvement in patients with severe malaria. This paper aim to discuss briefly about lung derangement in the severe malaria and the inflammatory response related to the lung dysfunction. The severity of pulmonary impairment due to complications of malaria is determined not only by the initiation of antimalarial treatment but also by the hosts associated immune response.

PERSISTENCE OF MALARIALANTIGEN FOLLOWING ANTIMALARIAL CHEMOTHERAPY IN KOLKATA, WEST BENGAL

Early diagnosis and complete treatment is one of the important aspects of malaria elimination programme worldwide. In many areas the diagnosis is based on detection of malarial antigen using commercially available rapid diagnostic kits. The problem remains with persistence of antigen following parasite clearance by proper treatment. The present work was undertaken to study the pattern of persistent antigen of P. vivax and P. falciparum following antimalarial treatment. Atotal of 300 microscopically positive mono-infected with P. vivax (160) and P. vivax (140) patients were recruited, treated with antimalarial drugs and followed up on day 3, 7, 14, 21 and 28 for persistent parasites and antigen. P. vivax specic pLDH antigen was disappeared from peripheral blood within 14 days post treatment period. P. falciparum specic HRP-2 antigen was persisted even after 28 days of treatment. Depending only on antigen based diagnosis, attention should be paid before treatment, particularly in areas with high malaria transmission

A randomized controlled trial of dihydroartemisinin-piperaquine, artesunate-mefloquine and extended artemether-lumefantrine treatments for malaria in pregnancy on the Thailand-Myanmar border

Background Artemisinin and artemisinin-based combination therapy (ACT) partner drug resistance in Plasmodium falciparum have spread across the Greater Mekong Subregion compromising antimalarial treatment. The current 3-day artemether-lumefantrine regimen has been associated with high treatment failure rates in pregnant women. Although ACTs are recommended for treating Plasmodium vivax malaria, no clinical trials in pregnancy have been reported. Methods Pregnant women with uncomplicated malaria on the Thailand-Myanmar border participated in an open-label randomized controlled trial comparing dihydroartemisinin-piperaquine (DP), artesunate-mefloquine (ASMQ) and a 4-day artemether-lumefantrine regimen (AL+). The primary endpoint for P. falciparum infections was the PCR-corrected cure rate and for P. vivax infections was recurrent parasitaemia, before delivery or day 63, whichever was longer, assessed by Kaplan-Meier estimate. Results Between February 2010 and August 2016, 511 pregnant women with malaria (353 P. vivax, 142 P. falciparum, 15 co-infections, 1 Plasmodium malariae) were randomized to either DP (n=170), ASMQ (n=169) or AL+ (n=172) treatments. Successful malaria elimination efforts in the region resulted in premature termination of the trial. The majority of women had recurrent malaria (mainly P. vivax relapses, which are not prevented by these treatments). Recurrence-free proportions (95% confidence interval [95% CI]) for vivax malaria were 20.6% (5.1–43.4) for DP (n=125), 46.0% (30.9–60.0) for ASMQ (n=117) and 28.7% (10.0–50.8) for AL+ (n=126). DP and ASMQ provided longer recurrence-free intervals. PCR-corrected cure rates (95% CI) for falciparum malaria were 93.7% (81.6–97.9) for DP (n=49), 79.6% (66.1–88.1) for AMSQ (n=55) and 87.5% (74.3–94.2) for AL+ (n=50). Overall 65% (85/130) of P. falciparum infections had Pfkelch13 propeller mutations which increased over time and recrudescence occurred almost exclusively in them; risk ratio 9.42 (95% CI 1.30–68.29). Among the women with falciparum malaria, 24.0% (95% CI 16.8–33.6) had P. vivax parasitaemia within 4 months. Nausea, vomiting, dizziness and sleep disturbance were more frequent with ASMQ. Miscarriage, small-for-gestational-age and preterm birth did not differ significantly among the treatment groups, including first trimester exposures (n=46). Conclusions DP was well tolerated and safe, and was the only drug providing satisfactory efficacy for P. falciparum-infected pregnant woman in this area of widespread artemisinin resistance. Vivax malaria recurrences are very common and warrant chloroquine prophylaxis after antimalarial treatment in this area. Trial registration ClinicalTrials.gov identifier NCT01054248, registered on 22 January 2010.

#11: Post-malarial Hemolysis is Rare in Malawian Children with Cerebral Malaria

Background In severe malaria, artesunate decreases mortality compared to quinine. Artesunate’s introduction into clinical use in malaria-endemic areas revealed a unique adverse effect: severe hemolysis appearing several weeks after treatment completion. Though initial reports of post-artesunate hemolysis (PAH) were gathered from adult returning travelers, studies of African children revealed that PAH was less common in this semi-immune population. There are no published studies establishing the incidence and severity of PAH in several severe malarial syndromes in African children, including cerebral malaria (CM). We determined the incidence and severity of post-treatment hemolysis in Malawian children surviving CM by analyzing hospital and follow-up data from a long-standing study of CM pathogenesis. Methods Children aged 6 months to 14 years admitted to Queen Elizabeth Central Hospital (Blantyre, Malawi) with a clinical diagnosis of CM were enrolled in a retrospective cohort study. Children admitted before 2014 and treated with quinine (n=258) were compared to those admitted in 2014 and after and treated with artesunate (n=235). Hematocrit and parasite density were obtained at admission and every 6 hours until parasite clearance. The last hematocrit obtained during hospitalization was compared with the one-month post-hospitalization hematocrit value. Results The overall rate of a post-hospitalization decrease in hematocrit in children surviving CM was 5.3% (4.7% for quinine, 5.8% for artesunate, p value for difference= 0.582); no patients with a hematocrit decrease were symptomatic; none required transfusion. Of the 26 children with a decrease in hematocrit at one month after hospitalization, 23.1% had evidence of a new malaria infection. When children treated with quinine and artesunate were combined, a higher hematocrit on admission, lower quantitative histidine rich protein 2 level, and splenomegaly were independently associated with a post-treatment decrease in hematocrit. Conclusions In African survivors of CM, post-treatment hemolysis is rare, mild, and unassociated with the antimalarial treatment received.

Association between ABCB1 Polymorphisms and Artesunate–Mefloquine Treatment Responses of Patients with Falciparum Malaria on the Thailand–Myanmar Border

A decrease in the clinical efficacy of a 3-day artesunate–mefloquine combination treatment was reported in the areas of multidrug-resistant Plasmodium falciparum along the Thailand–Myanmar border. The current study investigated the possible contribution of genetic polymorphisms of the three major genes encoding drug efflux transporters, ABCB1, ABCG2, and ABCC1, to responses to the aforementioned treatment in 91 patients with acute uncomplicated falciparum malaria residing along the Thailand–Myanmar border. Patients carrying homozygous mutant genotype ABCB1 c.1236C>T (TT) were found to have a three-times higher chance of successful treatment with this combination compared with other genotypes (CC and CT). Furthermore, whole blood mefloquine concentrations in these patients with the TT genotype were significantly lower than those of patients carrying the CC genotype. Patients with heterozygous mutant genotype (CT), however, were three-times more likely to experience treatment failure. No significant association was found with the ABCG2 and ABCC1 gene polymorphisms. The results suggest that ABCB1 c.1236CT polymorphisms could be useful genetic markers for predicting responses to the 3-day artesunate–mefloquine treatment; however, studies using larger sample sizes in different malaria-endemic areas are necessary to confirm this finding. This study highlights the impact of pharmacogenetic factors on antimalarial treatment responses and the basis for the application of control policies in various malaria-endemic areas.