Malaria parasite carbonic anhydrase:inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.

Antimalarial qinghaosu/artemisinin: The therapy worthy of a Nobel Prize

Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu(Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.

Association of ABO blood group and Plasmodium falciparum malaria in Dore Bafeno Area,Southern Ethiopia

Objective:To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum(P.falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center,Southern Ethiopia.Methods:A total of 269 febrile outpatients who visited Dore Bafeno Health Center,Southern Ethiopia,were examined for malaria and also tested for ABO blood groups in January 2010.The blood specimens were collected by finger pricking,stained with Geimsa,and examined microscopically.Positive cases of the parasitemia were counted.CareStart^(TM) Malaria PflPv Combo was also used to test the blood specimens for malaria.ABO blood groups were determined by agglutination test using ERYCLONE antisera.Data on socio-demographic characteristics and treatment status of the participants were also collected.Chi-square and ANOVA tests were used to assess the difference between frequencies and means,respectively.Results:Out of a total of 269 participants,178(66.2%) febrile patients were found to be infected with Plasmodium parasites,among which 146(54.3%),28(10.4%),and 4(1.5%) belonged to P.falciparum,P.vivax,and mixed infections,respectively.All febrile patients were also tested for ABO blood groups and 51.3%,23.5%,21.9%and 3.3%were found to be blood types of 0,A,B and AB,respectively.Both total malaria infection and P.falciparum infection showed significant association with blood types(P<0.05).The proportion of A or B but not 0 phenotypes was higher(P<0.05) in individuals with P.falciparum as compared with non-infected individuals.The chance of having P.falciparum infection in patients with blood groups A,B and AB was 2.5,2.5 and 3.3times more than individuals showing blood 0 phenotypes,respectively.The mean P.falciparum malaria parasitemia for blood groups A,B,AB,and 0 were 3 744/μ L,1 805/ μ L,5 331/μ L,and1 515/μ L,respectively(P<0.01).Conclusions:The present findings indicate that individuals of blood groups A,B and AB are more susceptible to P.falciparum infection as compared with individuals of blood group O.Nevertheless,further in depth studies are required to clearly establish the role that ABO blood group plays in P.falciparum malaria.

Demonstration of malaria situation analysis,stratification and planning in Minab District,southern Iran

Objective:To demonstrate malaria situation analysis,stratification and planning for an endemic area in southern Iran.Methods:Data on health system,population,meteorological parameters, malaria cases,anopheline vectors,and control activities during 2005-2007 was obtained from Minab Health Center,Minab Meteorological Station and published documents about malaria elements in the study area.A datasheet was created in excel 2003 for analysis.Results:There were 644 health staff working in Minab District including 99 health staff in malaria control program.The health facilities are distributed as follow:1 hospital with 96 beds,23 health centers including private centers(10 in Minab city and 13 in rural area of Minab District) and 119 health houses in rural areas of Minab District.Anopheles stephensi was the dominant species in Minab District,however,Anopheles dthali,Anopheles superpictus,Anopheles fluviatilis,Anopheles multicolor,Anopheles pulcherrimus and Anopheles turkhudi can also be found in the area. Anopheles stephensi was reported susceptible to malathion,propoxur,primphos-methyl,lambdacyhalothrin permethrin and deltamethrin,and resistant to DDT and dieldrin in the area.During the study period a total of 10 665 positive cases were reported,mainly due to local transmission (99.6%).Plasmodium vivax was the main causative agent followed by Plasmodium falciparum. There were reports about drug resistance of Plasmodium falciparum in the area.Conclusions: Using different parameters,Minab was classified into 3 strata.A plan was designed based on described goal,objectives and targets.The approaches of this plan were categorized into:health education,early detection and correct treatment,and vector control.Main constraints of these approaches are population movement between Iran,Pakistan and Afghanistan;vector control challenges at district,inadequate skilled medical staff in malaria case management and weak inter-sectorial coordination for malaria control,especially in urban areas.

China's foreign aid for global poverty alleviation:artemisinin-based combination therapies against malaria in Togo

From providing funds for the global fight against infectious diseases,to actively participating in global health security actions,to strengthening mutual cooperation in the field of health,and providing medical treatment,training and scholarships to countries in need,China’s foreign aid on global poverty alleviation is increasingly diversified and expanding in scale.Indeed,China is playing an increasingly important leading role in the global health agenda.It is worth mentioning that over the years,artemisinin compound have saved millions of lives all over the world,especially in poverty-stricken areas.China’s work mode of malaria elimination has also been written into WHO’s technical documents and recommended to other countries.Since 2007,Chinese medical staff has carried out the Artemisinin Compound Malaria Control Project in Comoros,bringing Chinese prevention and treatment programs to the local area.By 2014,Comoros had achieved zero deaths from malaria,and the number of cases had dropped by 98%.Now,this program is also extended to Togo,another African country.This article preliminarily summarizes the malaria profile in Togo and introduces China-Togo Cooperative Artemisinin Malaria Control Demonstration Project to provide a reference for better anti-malaria assistance in Togo,and also shows one of the substantive actions of China’s participation in global health governance,which contributes Chinese wisdom and offers Chinese solutions to global poverty alleviation.

Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries?

Artemisinin from the plant Artemisia annua （A. annua） L., and used as artemisinin combination therapy （ACT）, is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat “fever”. More recently, investiga-tors have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic effcacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and effcacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes （mainly mono and sesqui）, favonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. an-nua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T？ and Tmax and greater Cmax and AUC in Plasmodium chabaudi -infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were 〉 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. ACTs are still unaffordable for many malaria patients, and cost estimates for A. annua dried leaf tablet production are orders of magnitude less than for ACT, despite improvements in the production capacity. Considering that for 〉 2000 years this plant was used in traditional Chinese medicine for treatment of fever with no apparent appearance of artemisinin drug resistance, the evidence argues for inclusion of affordable A. annua dried leaf tablets into the arsenal of drugs to combat malaria and other artemisinin-susceptible diseases.

Influence of Weather and Climate on Malaria Occurrence Based on Human-Biometeorological Methods in Ondo State, Nigeria

This study focuses on the influence of weather and climate on malaria occurrence based on human-biometeorological methods was carried out in Ondo State, Nigeria using meteorological and malaria dataset in the state for the period from 1998 to 2008. In addition, sea surface temperatures （SSTs） over equatorial Pacific Ocean were integrated in the analysis. The association between each of the meteorological-biometeorological parameters and clinical-reported malaria cases was examined by using Poisson distribution and log as link function between the two categories of dataset. The next step was the building of a model by using Poisson multiple regression models （GLMs） in order to know the weather variables that lead to statistically changes in clinical-reported malaria cases. The study revealed that an increase of I m.s1 of wind speed can lead to an increase of about 164% and 171% in the monthly occurrence of malaria at 95% confidence interval in derived savanna and humid forest zone respectively. Also, an increase of I ℃ in air temperature and sea surface temperature is associated with 53.4% and 29% increase in monthly malaria occurrence （CI： 95%） in derived savanna while an increase of 1 ℃ in air temperature and sea surface temperature is associated with 56.4% and 15.4% increase in monthly malaria occurrence at 95% confidence interval in humid forest zone of Ondo State

The Influence of Climate/Weather to the Growth and Distribution of Malaria

More than million people die from malaria every year(Philippe Brasseur et al.,1999).Some studies indicate that there may be as many as 3 million deaths and above per year due to malaria.Up to 90%of which occur in Africa,and 90%are children under age of 5 years.WHO estimates that 40%of the World’s population is at risk of malaria(Victor Ojeanelo, 2007).Weather and climate have significant effects on the growth and distribution of malaria transmitting mosquitos.Rainfall and temperature limits the growth and development of Anopheles mosquito,which

Chemotherapy and drug resistance status of malaria parasite in northeast India

India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for】10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.

Childhood malaria in the Niger delta area of Nigeria:mothers/care givers'perception,definition and treatment practices

Objective:The objective of the study was to evaluate mothers/care givers perception of malaria,their treatment practices and the effects on the outcome of malaria.Methods:Four hundred and sixty children were enrolled and their mothers/care givers interviewed.The children were screened for malaria parasitaemia and there after,blood specimens were obtained for biochemical and haematological evaluation from those children who met the criteria and tested positive to P.falciparum parasites.Packed cell volume,electrolytes,urea, creatinine,plasma glucose,and serum bilirubin were analyzed.Results:A total of 460 children were studied, 233(50.7%) males and 227(49.3%) females.Mild malaria cases were 112(24.3%) and severe malaria 348(75.7%).Those who presented early 106(23.0%) and those who presented late 354(77.0%).Perception and definition of malaria as well as the treatment seeking behaviors vary significantly with the level of education of the mothers and care givers.Those without formal education 68(51.9%) wrongly perceived that the etiology of malaria can only be diagnosed by native doctors compared to those with primary six education 61 (26.5%) and junior secondary education 10(10.1%).Only 43(9.3%) gave the correct dose of chloroquine syrup to their sick children,while 32(7.0%) gave at sub optimal doses.Conclusion:Wrong perception of malaria especially the complicated malaria and wrong treatment practices are major contributory factors to the high mortality and morbidity of malaria in Nigeria.There is therefore a need for health education to correct the wrong ideas about the cause and treatment practices of malaria as part of malaria control programme.

Evolution of specific RNA aptamers via SELEX targeting recombinant human CD36 protein:A candidate therapeutic target in severe malaria

Objective:To isolate and characterize RNA aptamers that are specific to human CD36 protein using systematic evolution of ligands by exponential enrichment(SELEX)technology to identify candidates for adjunct therapy to reverse the binding of Plasmodiuminfected erythrocytes.Methods:RNA aptamers were isolated using nitrocellulose membrane-based SELEX and binding analysis was screened using an electrophoretic mobility shift assay and enzyme-linked oligonucleotide assay.Results:Thirteen cycles of nitrocellulose membrane-based SELEX yielded three aptamers(RC60,RC25,RC04)exhibiting high binding against CD36 protein as shown on electrophoretic mobility shift assay.The sequence analysis revealed a G-quadruplex sequence within all the isolated aptamers that might contribute to aptamer binding and thermodynamic stability.The specificity assay further showed that RC60 and RC25 were highly specific to CD36.The competitive inhibition assay demonstrated that RC60 and RC25 shared a similar binding epitope recognized by m Ab FA6-152,a specific monoclonal antibody against CD36.Conclusions:RC60 and RC25 are promising candidates as anticytoadherence for severe malaria adjunct therapy.

Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target

Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.

Mapping and Prevalence of Malaria Falciparum Patients with ACT Failed Therapy, in Hanura Public Health Center, Pesawaran, Lampung, Indonesia

Malaria is a public health issue that can cause death. According to the Indonesian Health Profile, in the year 2010, an estimated 45% of Indonesia’s population live in malaria-endemic areas. Pesawaran District is one of the malaria-endemic areas in Lampung province, whose Annual Parasite Incidence in 2010 and 2011 were 2.77 and 4.76 respectively. One of the factors that may inhibit the malaria control is Plasmodium resistance to antimalarial drugs. This study aims to conduct a mapping study and see the prevalence of ACT treatment failure, in Pesawaran District, Lampung Province, Indonesia. Data collection was performed at the Primary Health Centers (PHC) Hanura. A total of 69 samples according to the inclusion and exclusion criteria, the microscopic examination serially for 28 days was done. Microscopic examination performed on D0, D1, D2, D3, D7, D14, D28, and a complaint is found outside the schedule. Coordinates of patient house, determined using GPS. Based on observations, microscopic examination and spatial analysis, the prevalence of ACT treatment failure in patients with falcipaum malaria was 11.59%. The malaria falcifarum patient spread around the coast, that were near vector breeding places. There were five clusters of malaria falciparum patients and one cluster of malaria falciparum patient with treatment failure that were formed. Only one significant cluster of malaria falciparum patient (P = 0.0027, radius 0 km) is found, while the other cluster is not statistically significant. The cluster of malaria falciparum patient with treatment failure was not statistically significant (P = 1.000, radius 0.15 km), but this cluster is located in the area of the suspected vector breeding place. The cluster formation means that people living within a radius of these clusters have a greater risk to get malaria infection.

Fixed-Dose Combination (FDC) Formulation of Quinine Sulphate-Doxycycline (Qidox) for Malaria Therapy

Background: One of the deadliest parasite infections is malaria. A combination of quinine sulphate and doxycycline is another therapeutic option for malaria that is resistant to chloroquine and is anticipated to be able to both combat the issue of anti-malarial medication resistance as well as the compliance to malaria therapy that is still raging in certain locations of Indonesia. Aim: This study will focus on evaluating the possibility of interaction between quinine sulphate and doxycycline followed by formulating the fixed-dose combination of both active pharmaceutical ingredients. Method: The study was designed as a laboratory experiment and applied some examinations. The examination from the organoleptic test of active pharmaceutical ingredients powder, crystallography analysis, and physical analysis of fixed-dose tablet including hardness, friability, and disintegration time testing. Result: The crystallography study reported there was no physical interaction found between quinine sulphate and doxycycline. The formula found excellent tablet printability with a composition of Quinine sulphate and doxycycline (Qidox). Conclusion: quinine sulphate with doxycycline can be combined into one tablet as Fixed-Dose Combination (FDC).

Revisiting the Evaluation of the Effectiveness of Artemether-Lumefantrine Combination in the Treatment of Uncomplicated Malaria in Elele, a Malaria Endemic Area in Rivers State Nigeria

Background: The World Health Organization adopted Artenisinin based combination therapy (ACT) for the treatment of uncomplicated malaria in endemic regions. The efficacy of ACT in malaria treatment must have prompted this choice. There’s need to protect the ACT from plasmodial resistance. Hence, clinical scaling up of ACT program is needed. This entails continued assessment, monitoring and evaluation of the effectiveness of component drugs in endemic areas. Purpose: This study revisited the evaluation of the effectiveness of artemether-lumefantrine combination (ALC) in the treatment of uncomplicated malaria in Elele, Nigeria. Method: The study was conducted in Elele, a malaria endemic area in Rivers State, Nigeria. This was a facility based descriptive, cross sectional study at Madonna University Teaching Hospital (MUTH) Elele using simple sampling technique. Qualitative and quantitative data were collected. 100 patients who consented to the study were recruited in the outpatient clinic using semi structured questionnaires as part of study instrument. Inclusion criteria were having a body temperature of ≥37.5&deg;C, symptoms of malaria, positive parasitemia, non ingestion of antimalarial in the past 2 weeks, etc. MUTH ethics committee gave ethical clearance. Patient recruitment following consent commenced with their symptoms and signs recorded at presentation while disappearance of the same was determined following drug ingestion on days 2/4/6/8/10 and 14. The data gotten was analyzed by tallying the responses to get the frequencies using SPSS 16.0 version and Microsoft excel tools. The student t-test was used to calculate the P-value, values < 0.05 was considered statistically significant. Results: Most of the patients knew mosquitoes as the mode of malaria transmission (70%). The ACT is known and used by these patients: artesunate/amodiaquine: 41 (41%);artesunate/lumefantrine: 40 (40%);artesunate/sulphadoxine-pyrimethamine: 38(38%);artesunate/mefloquine: 20 (20%). Fever was the predominant presenting symptom, 92% followed by body weakness (90%);headache (85%);malaise (80%);loss of appetite (80%);nausea (72%);vomiting (70%);abdominal pains (50%). Others were: pallor (30%);hepatomegally (20%);splenomegally (20%);chills (20%);rigor (20%). By day 10 of therapy, fever, vomiting and abdominal pains had disappeared in all patients, some patients still had mild: body weakness 40%;headache 2%;malaise 24%;loss of appetite 20% and nausea 10%. Day 14 recorded no symptoms in all patients. There was effective clinical response (ECR) by day 14. Conclusion: This study hereby reaffirms the efficacy and effectiveness of Artemether-lumefantrine Combination in the treatment of uncomplicated malaria in Elele, Nigeria. The need to fill the existing knowledge gap of monitoring and evaluation of ACT in rural endemic areas has been done by this study.

CRX-527 as a candidate adjuvant in a recombinant BCG-based malaria vaccine

Objective:To investigate the role of CRX-527,a Toll-like receptor 4 agonist,as the possible adjuvant for recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing merozoite surface protein 1C(BCG-MSP-1C).Methods:The mice were immunized with BCG and BCG-MSP-1C in the presence and absence of CRX-527.The untreated mice(injected with PBS-T80 only)were the negative control.The ability of CRX-527 to enhance IgG and its subclasses,as well as IL-4 and IFN-γproduction in the serum and spleen supernatant was evaluated using ELISA.Results:Mice immunized with BCG-MSP-1C exhibited the highest production of IgGs,IL-4 and IFN-γafter third immunization.In addition,CRX-527 further promoted the production of total IgG and IgG subclasses as well as IFN-γand IL-4 in the serum and splenocytes of immunized mice.Conclusions:CRX-527 has the potential as an adjuvant candidate for the candidate vaccines.Further study is needed to verify appropriate dosage for immunization and its efficacy.

Investigation of the Role of ABC Transporters in Pyrethroids Resistance in the Major Malaria Vector Anopheles coluzzii from Northern Nigeria

Resistance to currently available insecticides in the major malaria vectors like Anopheles coluzzii is seriously reducing the effectiveness of core vector control tools. Overexpression of ATP binding cassette transporters (ABC transporters) has been implicated in insecticides resistance in the major malaria vector Anopheles funestus and An. gambiae. To identify the potential role of ABC transporters in pyrethroids resistance in this work, we use verapamil-a p-glycoprotein inhibitor in a synergist bioassay with pyrethroids on one An. coluzzii populations from northern Nigeria. Genomic DNA extraction and SINE 200 PCR established that the Anopheles s. l. from Auyo, Jigawa State was An. coluzzii. Pre-exposure to verapamil followed by Permethrin results in 0.12% knockdown after 1 hour exposure and 10.7% mortality after 24 hours, which was higher than that for permethrin alone, but not statistically significant. This bioassay result reveals that ABC transporters possibly do not contribute to the resistance.

Epidemiological, Clinical, Biological, Therapeutic Features and Outcome of Congenital Malaria at the Borgou Regional University Teaching Hospital (CHUD-B) in Benin in 2015

Background: The prevalence of congenital malaria is getting more and more significant in Sub-Saharan Africa where is a malaria-endemic area. This study aimed to identify the clinical and therapeutic features as well as the outcome of congenital malaria in CHUD-B in 2015. Method: It was a cohort and descriptive study with analytical purpose, carried out in the Mother and Child Department which includes the Gynecology & Obstetrics and Pediatric Unit of CHUD-B. The study target population consisted of all the infants born in the CHUD-B as well as their mothers. The main variable was the presence of congenital malaria. The independent variables were those related to clinical, therapeutic features and outcome. Results: In the study, among the 300 newborns registered, 57 carried congenital malaria i.e. a prevalence of 19%. 171 (57.0%) of them were males versus 129 (43.0%) females. Among the 281 mothers involved, 48 presented with malaria in pregnancy i.e. a prevalence of 17.0%. At the end of this research work, the factors associated with congenital malaria were fever in the 3rd quarter and malaria in pregnancy in the mother. Conclusion: Nearly one out of five infants born in the CHUD-B was carrier of congenital malaria and approximately one out six mothers presented with malaria detection during pregnancy. A method based on Polymerase Chain Reaction (PCR) should be implemented during the diagnosis in order to confirm malaria cases among both newborns and mothers.

Effect of Artemether Treatment on Plasma Lipid Profile in Malaria

This study was undertaken to assess the effect of artemether treatment on plasma lipid profile in malaria infection. While the importance of lipid to plasmodial infective processes and metabolism is being increasingly appreciated, little is known about the attendant effect of chemotherapy on plasma lipid profile. Thirty patients with uncomplicated malaria were chosen from two secondary health-care facilities in Yobe State, Nigeria with informed consents and ethical clearance. Based on predetermined inclusion criteria patients were given 3.2 mg/kg of artemether with 1.6 mg/kg on subsequent days for a total of five days. This was done after the collection of urine and blood samples for urinalysis, malaria parasite density count and serum lipid analysis. A follow-up was planned seven (7) days from first dose during when clinical assessment and repeat malaria parasite density count and serum lipid analysis were done. Data were analyzed with statistical package for social scientist and Microsoft Excel spread sheet while level of significance at p ≤ 0.05 was calculated using paired t-test. Serum HDL cholesterol concentration recorded a significant decline of 0.13 mmol/L from a pre-treatment mean concentration of 1.17 mmol/L (p < 0.04). Triglyceride, total cholesterol, LDL-cholesterol, VLDL-cholesterol showed increment or reductions that were not significant. The clinical cure rate was 50% and mean percentage reduction in parasitaemia was 52%. A possible explanation for this low cure rate could be resistance, unfavorable pharmacokinetic disposition or lack of full adherence. A trial with complete parasite clearance, possibly using artemisinin-based combinational therapy would provide a more compelling result.

Comparison of Efficacy and Safety of Artemisinin-Based Combination Therapies for Treating Uncomplicated Falciparum Malaria in Sub-Saharan African Countries: An Update on the Changes in Efficacy Using Network Meta-Analysis

Background: Several artemisinin-based combination therapies (ACT) are available to treat uncomplicated malaria in Africa. The present study aimed to assess the ranking of their efficacy and tolerance. Methods: A database of randomized controlled trials was retrieved from published papers. Network meta-analysis was used to compare efficacy on day 28 and day 42 after initiation of treatment. Age covariate effect on treatment outcome was assessed, and a modeling approach to reduce heterogeneity among trials was evaluated under the hypothesis of consistency in a meta-regression. Safety and adverse events were compared among different ACTs. A Bayesian analysis was performed to implement the consistency models using WinBUGS software. The results were compared to those of the frequentist approach using the R software. Results: Eighty-one articles, in which a total of 15 different ACTs were tested in more than 36,000 patients, were included. On day 28, dihydroartemisinin-piperaquine (DHPP) was more effective than artemether-lumefantrine (AL) before (odds ratio [OR], 1.83;95% confidence interval [CI], 1.31 - 2.56) and after age-covariate adjustment (OR, 1.70;95% CI, 1.20 - 2.43). The result was similar on day 42. DHPP occupied the top rank. The risk of having cough, diarrhoea or headache post-treatment was significantly lower with DHPP than AL. Artesunate-mefloquine (ASMQ) was associated with a significantly lower prevalence of vomiting or nausea (OR, 0.80;95% CI, 0.48 - 1.30) and headache (OR, 0.53;95% CI, 0.40 - 0.68) compared to AL. On the contrary, vomiting and nausea occurred more frequently after fixed-dose artesunate-amodiaquine formulation (ASAQf) than with AL (OR, 1.45;95% CI, 1.18 - 1.78). The risk of anaemia was higher with ASAQf and co-blistered artesunate-amodiaquine (ASAQc) than with AL. There was no significant difference in risk of anaemia (P > 0.05) between AL and different formulations of ASAQ. Conclusions: Based on the available evidence, this study demonstrated the superiority of DHPP, followed by AL, among currently recommended ACTs in terms of efficacy and tolerance. Network meta-analysis could be an alternative analytical tool but needs more data input from therapeutic efficacy studies. The determination of the best available therapy requires data triangulation and data science.