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Human immunodeficiency virus (HIV) infection affects body composition, but their relationship has not been studied in pregnant women. We conducted a cross-sectional study among 1669 women receiving antenatal care between 22 and 35 wk of gestation in Harare, Zimbabwe. The role of HIV-1 status and viral load, malaria and elevated serum alpha(1)-antichymotrypsin (ACT, an acute phase protein) in weight, body mass index (BMI), arm circumference (AC), triceps skinfold thickness (TSF), and arm muscle (AMA) and fat (AFA) area were assessed using multiple linear regression analysis. The mean (range) age was 24.4 (14-45) y and gestational age 29 (22-35) wk. HIV infection was present in 31.5% of the women, malaria parasitemia in 0.4% and 11.4% had serum ACT >0.4 g/L. There was no difference in any anthropometric variable between HIV-infected and uninfected women. However, women with viral loads (genome equivalents/mL) between 4 and 5 and >5 log(10) had 1.1 [95% confidence interval (CI): -0.3, 2.3] and 2.5 (95% CI: 0.1, 5.1) kg lower weights compared with uninfected women; this was explained by losses of both AFA and AMA. Malaria parasitemia was associated with 6 cm(2) (95% CI: 0.4; 11.8) or 25% lower AMA. Elevated serum ACT was a negative predictor of all anthropometric variables, i.e., levels between 0.3 and 0.4, 0.4 and 0.5 and >0.5 g/L were associated with 1, 2 and 6 kg lower mean body weights, respectively. Despite the limitations of a cross-sectional design, we conclude that arm fat and muscle areas, reflecting body fat and lean body mass, seem to be unaffected in the majority of HIV-infected pregnant women, but decline with increasing viral loads. The effects of viral load are not explained by elevated serum ACT, which is a strong independent predictor of all anthropometric variables.
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PMID:HIV-1 viral load and elevated serum alpha(1)-antichymotrypsin are independent predictors of body composition in pregnant Zimbabwean women. 1246 18

In terms of drug resistance Bangladesh acts as an important gateway to the Indian Subcontinent. However, little is known about the current status of drug resistance in this country. The aim of this study was therefore to determine the therapeutic efficacy as well as in vitro drug sensitivity of quinine for 3 days plus a single dose of sulfadoxine/pyrimethamine (Q3F), an affordable alternative to the previously used chloroquine, for the treatment of uncomplicated falciparum malaria. Sixty-three patients were enrolled in the study; the overall cure rate in a 42-day follow-up after PCR adjustment was 87.3% (95% CI: 77.6-94.1). One patient was classified as early treatment failure (1.7%, 95% CI: 0.0-8.9%); 6 patients (10%; 95% CI: 3.8-20.5%) had late treatment failures within a median time of 27 days. HRP2 in vitro drug sensitivity tests were performed on all samples. Significantly higher (P = 0.008) in vitro IC(50)s for pyrimethamine in treatment failures reflect the somewhat compromised drug sensitivity to this drug. These data suggest that the combination of 3 days of quinine with a single dose of sulfadoxine/pyrimethamine is an interesting and affordable alternative as long as or whenever ACT is not available.
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PMID:Therapeutic efficacy of quinine plus sulfadoxine-pyremethamine for the treatment of uncomplicated falciparum malaria in Bangladesh. 1703 87

Each year on the 25th April Africa and the rest of the world commemorate Africa Malaria Day as was agreed upon at the African Summit on Roll Back Malaria held in Abuja, Nigeria on 25th April 2000. The summit also called upon the United Nations to declare the period 2001-2010 a decade for malaria. The 1st Africa Malaria Day was commemorated with the theme "Communities Play a Central Role in Tackling Malaria". The 6th Africa Malaria Day was observed in 2006 with the theme "Get Your ACT Together" and the slogan "Universal Access to Effective Malaria Treatment is a Human Right". This article by the Secretariat of the Multilateral Initiative on Malaria (MIM) was also part of the commemorations for the day. MIM was founded in 1997 as an alliance of institutions and individuals concerned with the malaria problem, and aiming at maximizing the impact of scientific research on malaria through strengthening African research capacity and coordinated global collaboration. The MIM Secretariat has been hosted in rotation by the founding institutions, and is being hosted for the first time in Africa by the African Malaria Network Trust (AMANET) in Dar es Salaam, Tanzania. This article reviews the malaria situation in Africa six years after the Abuja Declaration, highlighting the disease burden trends, failures, achievements, challenges, and the way forward.
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PMID:Sixth Africa Malaria Day in 2006: how far have we come after the Abuja Declaration? 1709 Mar 8

Artemisia annua became a valuable agricultural crop after the World Health Organization recommended artemisinin as a component of ACT (artemisinin-combination based therapies) for malaria in 2001. A cloned, greenhouse-grown, A. annua (Artemis) subjected to an acidic soil and macronutrient deficit was evaluated for artemisinin production. Lack of lime (L) and macronutrients (N, P, and K) reduced leaf biomass accumulation. When L was provided (pH 5.1), the highest average leaf biomass was achieved with the "complete" (+N, +P, +K, and +L) treatment (70.3 g/plant), and the least biomass was achieved with the untreated (-N, -P, -K, and -L) treatment (6.18 g/plant). The nutrient least required for biomass accumulation per plant (g) was K (49.0 g), followed by P (36.5 g) and N (14.3 g). The artemisinin concentration (g/100 g) was significantly higher (75.5%) in -K plants when compared to plants under the complete treatment (1.62 vs 0.93%). Although the artemisinin total yield (g/plant) was 21% higher in -K plants, it was not significantly different from plants under the complete treatment (0.80 vs 0.66 g/plant). There were no marked treatment effects for concentration (g/100 g) or yield (g/plant) of both dihydroartemisinic acid and artemisinic acid, although higher levels were achieved in plants under the complete or -K treatments. There was a positive and significant correlation between artemisinin and both artemisinic acid and dihydroartemisin acid, in g/100 g and g/plant. This is the first report where potassium deficiency significantly increases the concentration (g/100 g) of artemisinin. Thus, under a mild potassium deficiency, A. annua farmers could achieve similar gains in artemisinin/ha, while saving on potassium fertilization, increasing the profitability of artemisinin production.
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PMID:Nutrient deficiency in the production of artemisinin, dihydroartemisinic acid, and artemisinic acid in Artemisia annua L. 1729 13

Sterile immunity against malaria can be achieved by the induction of IFNgamma-producing CD8(+) T cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (CSP). In the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the CD8(+) epitope of Plasmodium berghei CSP into the MHC class I presentation pathway, by either a type III secretion system of live recombinant Salmonella and/or by direct translocation of a recombinant Bordetella adenylate cyclase toxoid fusion (ACT-CSP) into the cytosol of professional antigen-presenting cells (APCs). A single intraperitoneal application of the recombinant ACT-CSP toxoid, as well as a single oral immunization with the Salmonella vaccine, induced a specific CD8(+) T cell response, which however conferred only a partial protection on mice against a subsequent sporozoite challenge. In contrast, a heterologous prime/boost vaccination with the live Salmonella followed by ACT-CSP led to a significant enhancement of the CSP-specific T cell response and induced complete protection in all vaccinated mice.
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PMID:Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid. 1880 38

Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based management of malaria. The accuracy of an RDT for the detection of clinical malaria and the presence of malarial parasites has recently been evaluated in a high-transmission area of southern Mali. During the same study, the cost-effectiveness of a 'test-and-treat' strategy for the home-based management of malaria (based on an artemisinin-combination therapy) was compared with that of a 'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been considered a presumptive case of uncomplicated malaria by a village healthworker, were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity, and positive and negative predictive values of this test, compared with the results of microscopy and two different definitions of clinical malaria, were then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the detection of parasites by microscopy. In the detection of clinical malaria, it was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%) sensitive but only 30.2% (24.8%-36.2%) specific when compared against the fulfillment of the World Health Organization's (2003) research criteria for uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and-treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0. v. U.S.$0.5). In older subjects, however, the two strategies were equally costly (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs. The question remains whether either of the strategies investigated can be made affordable for the affected population.
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PMID:Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area. 1917 72

There are several clinically useful endoperoxides, mainly artemisinin derivatives available in market for the treatment of malaria. These are highly potent drugs, with fastest parasite reduction ratio, broadest parasite stage specificity and effectiveness against all species of plasmodium in human. Endoperoxides are crystalline compounds having poor aqueous solubility. Several theories have been proposed for their mechanism of action, but the understanding is still incomplete. The major limitation of this class of compounds is the short half-life, requiring frequent administration, leading to noncompliance and recrudescence. Therefore, WHO recommends their use in combination with long acting antimalarial drugs (Artemisinin based combination therapy, ACT) to manage drug resistance, recrudescence, and non compliance. Endoperoxide compounds bind selectively to malaria-infected red blood cells and moderately to human plasma proteins. Artemisinin derivatives are converted primarily to the bioactive metabolite dihydroartemisinin after parenteral, oral or rectal administration. The rate of conversion is lowest for artelinic acid and highest for the water-soluble artesunate. Such conversion occurs largely in the liver by CYP enzymes. Oral bioavailability in animals ranges between 19 to 35%. Based on their liphophilicity, they tend to cross the blood-brain barrier, causing neurotoxicity in animal models. Efforts have been made to understand and develop pharmacokinetic-pharmacodynamic (PK-PD) correlation and identify PK-PD indices of endoperoxides. In the absence of the above, the selection of doses in ACTs has been empirical. There are several reports on clinical pharmacokinetic interactions of endoperoxides and their long acting partner drugs but as on date no clinically significant interaction has been reported. This review is an update on physicochemical, pharmacokinetic and pharmacodynamic properties of the endoperoxide antimalarials.
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PMID:Pharmacokinetics and pharmacodynamics of endoperoxide antimalarials. 1944 90

Chloroquine resistance in Plasmodium malaria is an emerging problem globally. In India resistance of Plasmodium falciparum to choloroquine, the cheapest and the most used drug was first reported in the year 1973 from Diphu of Karbi-Anglong district in Assam state. Systematic monitoring of drug resistance is being undertaken in the country from 1978 by the Directorate of National Vector Borne Disease Control Programme (NVBDCP) through its 13 Pf monitoring teams. The findings of these drug resistance studies has helped the programme for the revision of the drug policy and update it from time to time thereby facilitating appropriate measures for not only individual cases but also to contain and prevent further spread of resistant foci. This article summarises therapeutic efficacy studies conducted by the Pf monitoring teams in the country between 2001 and 2007 related to efficacy of chloroquine and other antimalarials drugs. As per the results available, the efficacy of chloroquine for treating uncomplicated falciparum at most of the study sites is much lower than the desired cut off levels of 10% (83% studies have shown treatment failure more than 10%). Total of 4273, 168 and 137 P. falciparum cases have been tested against chloroquine, sulphadoxine/pyrimethamine and ACT(AS+SP) combination. During the period under report, 85 new chloroquine resistant PHCs/foci from 64 districts were qualified warranting change of drug policy as per the national guidelines. These studies show that chloroquine resistance in P. falciparum is widespread in the country. To combat the drug resistant in malaria, the use of combination therapy ie, artesunate plus sulfadoxine/pyrimethamine has been recommended for treatment of all confirmed P. falciparum cases in all the qualified areas as per the criteria laid down in National Drug Policy on malaria.
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PMID:Emergence of drug resistance in India. 1955 4

In only five simple steps and 48% overall yield from the natural trioxane artemisinin, the thermally and hydrolytically stable trioxane fluoroanilide 4b has been prepared. Upon one oral dose of only 6.8 mg/kg of monomeric trioxane 4b combined with 20 mg/kg of mefloquine hydrochloride, all of the malaria-infected mice lived until at least day 30 post infection. Of the five mice in this surviving group, four (80%) were completely cured (no parasites in their blood) and one mouse had 4% blood parasitemia. Importantly, the efficacy of this ACT chemotherapy using monomeric trioxane 4b plus mefloquine hydrochloride is considerably better than the efficacy under the same conditions using the popular trioxane drug artemether plus mefloquine hydrochloride.
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PMID:Malaria-infected mice live until at least day 30 after a new monomeric trioxane combined with mefloquine are administered together in a single low oral dose. 1958 52

Lyells syndrome also called Toxic epidermal necrolysis is the extreme form of idiosyncratic drug reaction that is called Steven Johnsons Syndrome: The condition results in an extensive loss of the skin with mucous membrane involvement. Lyells syndrome has been induced by many agents. The commonest agent in the literature being sulphonamides. However, in our search of the medical literature there was no report of dihydroarthemisinin as a cause of Lyells syndrome. We report three patients seen at two tertiary health institutions with Lyells syndrome after treatment for malaria with dihydroarthemisinin. This resulted from administration of dihydroarthemisinin with chloroquine in two patients and dihydroarthemisinin with Amodiaquine in one patient. The first patient was a seven year old child who developed 90% cutaneous involvement and died from hemorrhagic shock. The second was a 28 old female that developed a 76% body surface involvement and died from septicemia. The third patient was a pregnant 37 year old woman that developed 52% body involvement and died from septic shock. In these patients the earliest symptoms were not recognized and there was considerable delay before referral. In view of the recent WHO recommendation ofArthemisinin Combination Treatment (ACT) for malaria, we expect more cases of Steven Johnson Syndrome and Lyells syndrome from ACT treatment. The aim of this report is to raise the awareness of clinicians to this potentially fatal complication.
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PMID:Severe idiosyncratic drug reaction (Lyells syndrome) after ingesting dihydroartemisinin. 1976 82


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