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The MalariaWorld Journal

Research: Buthionine sulfoximine increases the efficacy of arteether antimalarial activity in arteether-resistant Plasmodium vinckei by glutathione depletion

April 30, 2015 - 07:57 -- Bart G.J. Knols
Author(s): 
Ramesh Chandra, Santosh Kumar, Sunil Kumar Puri
Reference: 
MWJ 2015, 6, 4
 
We tested in vivo effects of L-buthionine (S,R)-sulfoximine (BSO) on glutathione (GSH) and hemozoin formation in arteether-sensitive and - resistant strains of Plasmodium vinckei. Groups of 7-8 Swiss mice were inoculated by intraperitoneal injection (i.p.) with 1×106 parasitized erythrocytes of PvAS (sensitive) or PvAR (resistant) strain of P. vinckei. The infected mice were treated with BSO (Sigma) 400 mg/kg twice a day for four days and blood was collected after the last injection with BSO. A relatively stronger inhibition of GSH level was observed in the blood of mice infected with resistant parasites (62.64%; p<0.0001), whereas inhibition in sensitive strain-infected mice and uninfected mice was 32% (p=0.034) and 35% (p=0.034), respectively. The results also show an inverse relationship between GSH and hemozoin in the arteether-sensitive and -resistant strains. The hemozoin contents in the resistant strain are 0.27±0.09, 0.69±0.14 and 5.30±0.79 μmol/109 cells at 5, 10 and 20% parasitemia, respectively, whereas hemozoin contents in the sensitive strain at the same parasitemia levels are 0.59±0.29, 12.38±1.96 and 30.80±2.27 μmol/109 cells. Moreover, hemozoin formation increased by 80% through the administration of BSO in the arteether-resistant strain, whereas insignificant changes occurred in the sensitive strain. BSO was also found to increase the efficacy of arteether antimalarial activity against the resistant strain in vivo. It is concluded that treatment with BSO significantly reduces the level of GSH, which leads to insufficient growth of resistant parasites. These results suggest that BSO might be helpful in prolonging the persistence of the drug, and pose a promising lead to help reducing the chance of resistance development against artemisinin and its derivatives.
 
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Research: Inhibitory effect of deltorphin-II on development of malaria in Plasmodium berghei-infected mice

March 23, 2015 - 21:47 -- Bart G.J. Knols
Author(s): 
Garasiya A. Ajitbhai, Prati P. Singh, Mukesh Kumar, Rajinder Singh, Vandana Dhiman
Reference: 
MWJ2015, 6, 3
Drug resistance has been one of the main obstacles in the fight against vector-borne infectious diseases. Among these diseases, malaria represents a serious public health challenge, mainly in the tropics, where vector-favourable climates are a crucial factor. Each of the various anti-malarial drugs currently used against this disease, such as quinolones, sulphonamides and artemisinins are inadequate and new strategies are required. Peptides are known to have a huge number of biological effects. Antimicrobial peptides (AMPs) have been proven to be effective against bacterial, fungal and viral infections. This study explored the effect of the peptide ‘deltorphin-II’ in Plasmodium berghei-infected mice. Mean percentage parasitaemia was calculated by studying infected erythrocytes after microscopic examination of 104 erythrocytes from infected mice on days 4, 7, 10, 14 and 21 after infection in all groups. Deltorphin-II shows maximum activity at a dose of 0.8 mg/kg/day from day 4 to day 21. Pre-treatment of infected mice with naltriben abrogates the deltorphin-II-mediated effect. Deltorphin-II inhibits the development of malaria, most probably via activation of the δ2 receptor.

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3.5
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Research: Willingness to accept malaria vaccine among caregivers of under-5 children in Ibadan North Local Government Area, Nigeria

March 23, 2015 - 21:28 -- Bart G.J. Knols
Author(s): 
Beliretu I Abdulkadir, Ikeoluwapo O Ajayi
Reference: 
MWJ2015, 6, 2
 
A malaria vaccine is a potentially effective addition to the armamentarium for malaria control. The candidate RTS,S malaria vaccine has undergone phase III clinical trials and WHO has indicated that a policy recommendation is possible in 2015. Given the delays with adoption of other novel interventions including vaccines, there is a need to ensure that all elements that will inform the decision to adopt a malaria vaccine, including community willingness, will be available on time. This study was carried out to assess the willingness of caregivers of under-5 children to accept a malaria vaccine once available and recommended for use. 427 consenting caregivers, selected using a cluster sampling technique, from five communities in Ibadan, Nigeria, participated in a questionnaire. In-depth interviews (IDIs) were conducted among 47 key community members. Data were analysed using descriptive statistics, Chi-square and logistic regression at p≤0.05. Thematic content analysis was used to analyse the transcribed IDI data. The mean age of survey respondents was 29.8±5.8 years. Only 20.1% of the respondents had ever heard of malaria vaccine; 87.0% showed willingness to accept a malaria vaccine. Reasons stated for not willing included ‘husband did not want immunisation’ (73.6%), ‘felt it might be expensive’ (47.2%) and ‘felt it might paralyse children’ (24.5%). Nearly half (48.7%) of the respondents said that if vaccine is not given orally like polio vaccine it might not be accepted. Influence of community health workers was found to predict willingness to accept a malaria vaccine (OR: 0.316, 95% CI: 0.142-0.705). IDI participants were favourably disposed to introduction of a vaccine against malaria, although they had concerns about the formulation of the vaccine and possible adverse events. Well-designed communication strategies implemented prior to the introduction of a malaria vaccine would be essential to foster a supportive environment for eventual adoption and acceptance thereof. 

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Research: Large-scale production of the malaria vector biocontrol agent Romanomermis iyengari (Nematoda: Mermithidae) in Benin, West Africa

January 17, 2015 - 15:13 -- Bart G.J. Knols
Author(s): 
Thiery BC Alavo, Ayaba Z Abagli, Rafael Pérez-Pacheco, Edward G Platzer
Reference: 
MWJ2015, 6, 1

The mermithid nematode Romanomermis iyengari is one of several natural control alternatives to synthetic pesticides for mosquito suppression. The commonly used mass rearing procedure of R. iyengari involves the use of coarse sand as a substrate for nematode maturation and oviposition. The coarse sand technique gives excellent nematode productivity in North America. However, under West African climatic conditions, this technique generates relatively lesser amounts of infectious worms. We evaluated coconut coir fibres as a replacement for coarse sand to improve yields in large-scale production of R. iyengari in Benin, West Africa. Culex quinquefasciatus was the host for the nematodes, and mosquitoes were blood-fed on chickens. Four days after blood feeding, egg rafts were collected and transferred into trays, each containing 2 l of water. The mosquito larvae were fed with fish food. When the mosquito larvae reached the second instar, preparasites (J2) were added (3 J2/larva) to the incubation trays. Eight days after infection, post-parasitic juveniles were separated from the water containing dead mosquito larvae and other debris using sieves and needles; 2 g of them were deposited in containers with coarse sand or coconut coir fibres and water. Three hours later, the water was drained, the jars covered and stored for eight weeks, after which J2 abundance was determined, using a total of 320 containers for each substrate. The abundance of J2 preparasites was also assessed 3-5 months after storage to determine the impact of long-term storage on the J2 yield. Results. After 2 months storage, 2 g of post-parasites (~457 females and 583 males) yielded an average of 559,300±6094 J2 and 155,818±4427 J2 per container for coconut fibres and for coarse sand, respectively. During long-term storage, yields of J2 on coconut fibres substrate slowly decreased from 442,180±9322 J2 (3 months storage) to 163,632±12,416 J2 per container (5 months storage). On coarse sand substrate, the yield was relatively low and decreased from 49,812±1200 J2 at 3 months storage to 3046±229 J2 at 5 months storage. Under West African climatic conditions, coconut coir fibres gave significantly higher preparasitic nematode yields than the coarse sand technique. 

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3.5
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Research: Performance and clinical usefulness of the Optimal-IT® test in the treatment of confirmed malaria cases in rural areas in Côte d’Ivoire

December 4, 2014 - 18:00 -- Bart G.J. Knols
Author(s): 
Yapo T. Aba, Emmanuel Bissagnené, Ouffoué Kra, Serge B. Assi, Raoul Moh, Pulchérie Goly, Nogbou Ello, Alain Kassi, Bessy R. Yao, Franklin Abouo, Eboi Ehui
Reference: 
MWJ2014, 5, 12

This study aimed at determining the performances of the Optimal-IT® test in the strategy for the exclusive treatment of uncomplicated malaria in rural areas in the forest region of San Pedro, Côte d’Ivoire. Patients exhibiting clinical signs of uncomplicated malaria who gave their consent benefited from thick blood film (TBF), blood smear (BS) and Optimal-IT® (pLDH-based) tests. Rapid diagnostic test (RDT) results were taken into consideration to decide on malaria treatment and then compared with TBF/BS results (reference) to assess the performances and clinical usefulness of the RDT. TBF/BS and Optimal-IT® were concordant in 92% of patients but discordant in 10 false negative (3%) and 19 false- positive patients (5%). The performances calculated were: sensitivity=95%, specificity=91%, positive predictive value=90%, negative predictive value=95%, positive likelihood ratio=10, negative likelihood ratio=0.06 and diagnostic odds ratio=166, indicating that Optimal-IT® is a powerful and credible diagnostic tool. The Optimal-IT® test, which is already used in the field, showed good performances to effectively detect patients with and without malaria. It is therefore adapted to the malaria treatment strategy limited to confirmed cases. 

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Research: HPLC separation and in vitro antimalarial studies of Artemisia annua plants from two different origins: Cameroon versus Luxembourg

November 16, 2014 - 12:30 -- Bart G.J. Knols
Author(s): 
Mutaz Akkawi, Suhair Jaber, Saleh Abu-Lafi, Mutaz Qutob, Qassem Abu-Rmeleh, Pierre Lutgen
Reference: 
MWJ2014, 5, 11

The search for new antimalarial drugs is urgently needed, especially drugs that can impede the heme detoxification pathway in the malaria parasite, a crucial requirement for parasite survival in host erythrocytes. Water infusions of Artemisia annua plants from two different origins, Cameroon and Luxembourg, were used in this study. Extracts from the leaves of the Cameroon plant showed a higher potential antimalarial activity, represented by a higher ability to inhibit β-haematin formation in vitro than A. annua extracts from Luxembourg. Although extracts of the plants of both origins showed comparable efficiencies at high concentrations, the absorbance value at 405 nm of a 10% dilution of the Cameroon plant extract was 0.075, whereas it was 1.515 for the Luxembourg plant extract. The absorbance is inversely proportional to the antimalarial activity. According to the Prep-HPLC chromatogram of the Cameroon crude sample, seven major compounds at 325 nm were found. However, only four much less pronounced compounds appeared in the Luxembourg crude sample under the same chromatographic conditions and concentration. These were preliminarily identified as polyphenolic compounds. A. annua infusions are widely used by people who cannot afford other treatments. Depending on the cultivation locality different chemical profiles exist. This results in differences in hemozoin formation and will therefore also lead to alterations in antimalarial activity.

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Research: Enabling factors facilitating the use of neem-based remedies for the management of malaria in the Lower Shire District of Chikwawa, Malawi

October 2, 2014 - 16:18 -- Bart G.J. Knols
Author(s): 
Edson Dembo, Fraction Dzinjalamala, Annette Habluetzel
Reference: 
MWJ2014, 5, 10

This study aimed to determine factors that facilitate the use of herbal remedies within communities in the management of malaria in the presence of free health care services,with the intention of assessing the feasibility of developing improved herbal products as anti-malarial prophylaxis. Data on factors driving the use of neem-based preparations commonly used in the management of malaria were collected through qualitative interviews and focus group discussions. Neem and moringa were identified as the principal plants used for the management of malaria. Factors favouring the communal use of neem-based remedies included the habit of resorting to herbal remedies as first aid treatment, lack of drugs and proper medical care in modern health facilities, and the need for preventive anti-malarial remedies during the high-transmission season. The perceived effectiveness of neem-based herbal remedies was based on their fast action against the symptoms of malaria, thereby providing immediate relief to the patient, which might explain their wide-scale use for malaria treatment. Local communities prefer to use neem and/or moringa remedies for their primary healthcare needs in the management of malaria because of their ease of access, preparation and administration without frequent adverse events, as opposed to ACTs. These remedies are already being used as prophylaxis in unimproved/non-standardised formulation. This suggests that standardised herbal preparations would be culturally acceptable at community level. Evidence-based research is required to validate parasitological and clinical efficacy and determine safety of these anti-malarial herbs.

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Research: The current status of infrastructure for monitoring the efficacy of antimalarial therapeutics in Zambia

September 23, 2014 - 13:54 -- Bart G.J. Knols
Author(s): 
Ellah Zingani, Satoshi Inoue, Lungwani Tyson M. Muungo
Reference: 
MWJ2014, 5, 9
 
The purpose of this study was to evaluate the current status of malaria diagnosis and treatment, and to monitor the therapeutic efficacy of antimalarial drugs. A descriptive cross-sectional survey was conducted from 2011 to 2013 at 10 district hospitals in Zambia designated as malaria sentinel sites as well as at the National Malaria Control Centre. Although basic infrastructure necessary for monitoring antimalarial drug resistance (such as laboratory, dispensary, admission ward, database unit, administration offices, bed space, examination and emergency rooms) was present at all sites, there was a shortage of licensed healthcare personnel. At some sites, antimalarial drugs were prescribed for malaria-like symptoms without diagnostic confirmation by blood smear. There was no regular monitoring of antimalarial drug resistance: only one trial was conducted among all sites in the previous 24 months. A lack of antimalarial drug resistance monitoring might be associated with personnel and funding shortages. Additional financial support would be necessary to avoid the development and spread of drug-resistant malaria in Zambia.

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Research: Economic aspects of suppressing malaria in Africa

September 22, 2014 - 13:59 -- Bart G.J. Knols
Author(s): 
William R. Jobin
Reference: 
MWJ2014, 5, 8
 
The purpose of this study was to determine whether investments in suppressing malaria might produce significant benefits for African nations. Two epidemiologic analyses wereused in parallel to evaluate data from Africa: a before-after comparison of countries treated under the US President’s Malaria Initiative for Africa (PMI), and a simultaneous comparison of treated-untreated countries. From 2007 to 2012, relative increases in population and gross domestic product (GDP) were greater in 14 countries treated as part of PMI than in 9 similar, but untreated countries. In the treated countries the relative increase in the GDP of 0.61 before malaria suppression rose to 0.64 afterwards; whereas in the untreated countries it fell from 0.67 to 0.56. The increase in GDP in the 14 treated countries that was attributable to malaria suppression over the 5-year interval was about $4.77 billion. During that period, the mean cost of suppressing malaria had been about $1.43 billion, indicating a return on the investment of 3.4 to 1. However, the costs began rising steeply in 2012. Malaria suppression might be worthwhile for African countries to undertake themselves, as long as the biocides and drugs in current use remain effective.

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Research: How well do malaria tests correlate with disease severity? Comparison of parasite density in children with mild and severe malaria

June 26, 2014 - 14:42 -- Bart G.J. Knols
Author(s): 
Sarah N. Kituyi, Nancy Nyakoe, Joseph N. Ngeranwa, Steven Runo, John N. Waitumbi
Reference: 
MWJ 2014, 5, 7
 
This study determined how well parasite density estimates by microscopy, qPCR and PfHRP-2 correlate to malaria severity. Patients aged ≤ 5 yrs with severe (n = 60, Hb ≤ 6 g/dl) and mild (n = 60, Hb > 6 g/dl) malaria were enrolled to take part in a case control study at Kisumu District Hospital, Western Kenya. Parasite load was determined by microscopy, qPCR targeting the 18s rRNA gene and PfHRP-2 antigen ELISA. The median parasite load and the 25th and the 75th percentile by microscopy in children with severe malaria (SM) was 49,958 parasites/μl (12,013-128,695) compared to 24,233 (6,122-103,886) in the group with mild malaria (MM), P = 0.10. By qPCR, the translated median parasite density was 31,550 parasites/μl (4,106-196,640) in the SM group compared to 24,365 parasites/μl (5,512-93,401) in the MM group (P = 0.73). According to PfHRP-2, the translated median parasite load in children with SM was 628,775 parasites/μl (332,222-1.165x106) compared to 150,453 (94,292-399,100) in children with MM (P < 0.0001). Unlike microscopy and qPCR, the parasite load detected by PfHRP-2 correlates with disease severity. Because of its unique attributes, PfHRP-2 is able to account for trophozoites and schizonts that are sequestered away from peripheral circulation. Because it persists in circulation, it also serves as an indicator of the magnitude of current and recent infections.

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