Comparison of Mycotoxin Contamination levels of Local and Imported Corn in Iraq

The study included determining pollution level of mycotoxin (aflatoxin, Ochratoxin, T2 / HT2) in local and imported corn in Iraq because it causes health damage and economic losses. In this study, 100 samples were collected from 50 samples of local corn, and 50 samples of imported corn and assed for mycotoxins test using ELISA technique and the results indicated the presence of the highest infection rates of mycotoxin in the local corn especially aflatoxin, where 28 sample at 56% were ranged between (20.1 - 157) ppb, which is higher than the allowable limits and 22 samples at (44%) were ranged between (5.1 to 2.9) ppb which is within the allowable limits , T2 / HT2 in 16 samples at (32%) of the total samples recorded less than (150) PPb which ranged between lowest value (25.8) ppb and the highest value (74.5) ppb and 34 samples at 68% with the value(0.0)ppb were is within the allowable limits, Ochratoxin, in 33 sample at 66% of the total samples less than(15) PPb recorded readings were  ranged between lowest value (1.5) ppb and the highest value (14.3) ppb, and 17 samples at  34% with the value (0.0)ppb,  which is also within the allowable limits in our country. Imported corn recorded readings in 24 samples at 48% as found by the three toxins and ranged the results of aflatoxin between the lowest value (0.8) PPb and the highest value (5.6) ppb and 26 samples at 52% with the value (0.0)ppb and T2 / HT2 results were ranged between the lowest value (3.1) ppb and the highest value (148) ppb and 26 samples at 52% with the value (0.0) ppb ochratoxin results were ranged between the lowest value (1.1) ppb and the highest value (5.7) ppb, and 26 samples at 52% with the value (0.0)ppb   and all of these results are within the allowable limits in our country. So we conclude from this study that the local corn was highest mycotoxin contamination than imported corn

Associations between Season and Gametocyte Dynamics in Chronic Plasmodium falciparum Infections

Introduction: In a markedly seasonal malaria setting, the transition from the transmission-free dry season to the transmission season depends on the resurgence of the mosquito population following the start of annual rains. The sudden onset of malaria outbreaks at the start of the transmission season suggests that parasites persist during the dry season and respond to either the reappearance of vectors, or correlated events, by increasing the production of transmission stages. Here, we investigate whether Plasmodium falciparum gametocyte density and the correlation between gametocyte density and parasite density show seasonal variation in chronic (largely asymptomatic) carriers in eastern Sudan. Materials and Methods: We recruited and treated 123 malaria patients in the transmission season 2001. We then followed them monthly during four distinct consecutive epidemiological seasons: transmission season 1, transmission-free season, pre-clinical period, and transmission season 2. In samples collected from 25 participants who fulfilled the selection criteria of the current analysis, we used quantitative PCR (qPCR) and RT-qPCR to quantify parasite and gametocyte densities, respectively. Results and Discussion: We observed a significant increase in gametocyte density and a significantly steeper positive correlation between gametocyte density and total parasite density during the pre-clinical period compared to the preceding transmission-free season. However, there was no corresponding increase in the density or prevalence of total parasites or gametocyte prevalence. The increase in gametocyte production during the pre-clinical period supports the hypothesis that P. falciparum may respond to environmental cues, such as mosquito biting, to modulate its transmission strategy. Thus, seasonal changes may be important to ignite transmission in unstable-malaria settings

Drug coverage in treatment of malaria and the consequences for resistance evolution - evidence from the use of sulphadoxine/pyrimethamine

BACKGROUND\ud \ud It is argued that, the efficacy of anti-malarials could be prolonged through policy-mediated reductions in drug pressure, but gathering evidence of the relationship between policy, treatment practice, drug pressure and the evolution of resistance in the field is challenging. Mathematical models indicate that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes.\ud \ud METHODS\ud \ud To test these predictions, dhfr and dhps frequency changes were measured during 2000-2001 while SP was the second-line treatment and contrasted these with changes during 2001-2002 when SP was used for first-line therapy. Annual cross sectional community surveys carried out before, during and after the policy switch in 2001 were used to collect samples. Genetic analysis of SP resistance genes was carried out on 4,950 Plasmodium falciparum infections and the selection pressure under the two policies compared.\ud \ud RESULTS\ud \ud The influence of policy on the parasite reservoir was profound. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr (N51I,C59R,S108N) allele (conferring pyrimethamine resistance) increased by 37% - 63% and the frequency of the double A437G, K540E mutant dhps allele (conferring sulphadoxine resistance) increased 200%-300%. A strong association between these unlinked alleles also emerged, confirming that they are co-selected by SP.\ud \ud CONCLUSION\ud \ud The national policy change brought about a shift in treatment practice and the resulting increase in coverage had a substantial impact on drug pressure. The selection applied by first-line use is strong enough to overcome recombination pressure and create significant linkage disequilibrium between the unlinked genetic determinants of pyrimethamine and sulphadoxine resistance, showing that recombination is no barrier to the emergence of resistance to combination treatments when they are used as the first-line malaria therapy

Resistance of a Rodent Malaria Parasite to a Thymidylate Synthase Inhibitor Induces an Apoptotic Parasite Death and Imposes a Huge Cost of Fitness

BACKGROUND: The greatest impediment to effective malaria control is drug resistance in Plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy. METHODOLOGY/PRINCIPAL FINDINGS: To generate resistance, P. berghei NK65 was subjected to 5-fluoroorotate (FOA, an inhibitor of thymidylate synthase, TS) pressure in mice. After 15 generations of drug pressure, the 2% DT (the delay time for proliferation of parasites to 2% parasitaemia, relative to untreated wild-type controls) reduced from 8 days to 4, equalling the controls. Drug sensitivity studies confirmed that FOA-resistance was stable. During serial passaging in the absence of drug, resistant parasite maintained low growth rates (parasitaemia, 15.5%±2.9, 7 dpi) relative to the wild-type (45.6%±8.4), translating into resistance cost of fitness of 66.0%. The resistant parasite showed an apoptosis-like death, as confirmed by light and transmission electron microscopy and corroborated by oligonucleosomal DNA fragmentation. CONCLUSIONS/SIGNIFICANCE: The resistant parasite was less fit than the wild-type, which implies that in the absence of drug pressure in the field, the wild-type alleles may expand and allow drugs withdrawn due to resistance to be reintroduced. FOA resistance led to depleted dTTP pools, causing thymineless parasite death via apoptosis. This supports the tenet that unicellular eukaryotes, like metazoans, also undergo apoptosis. This is the first report where resistance to a chemical stimulus and not the stimulus itself is shown to induce apoptosis in a unicellular parasite. This finding is relevant in cancer therapy, since thymineless cell death induced by resistance to TS-inhibitors can further be optimized via inhibition of pyrimidine salvage enzymes, thus providing a synergistic impact. We conclude that since apoptosis is a process that can be pharmacologically modulated, the parasite's apoptotic machinery may be exploited as a novel drug target in malaria and other protozoan diseases of medical importance

High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1.

Polymorphisms were examined in 2 Plasmodium falciparum genes, as were chloroquine responses of clones and isolates from a village in eastern Sudan. There was a significant association between an allele of the P. falciparum chloroquine resistance transporter gene (pfcrt-T76) and both in vitro and in vivo resistance. There was a less significant association with the multidrug resistance gene pfmdr1-Y86 allele. A significant association between pfmdr1-Y86 and pfcrt-T76 was apparent among resistant isolates, which suggests a joint action of the 2 genes in high-level chloroquine resistance

Population dynamics of Plasmodium falciparum in an unstable malaria area of eastern Sudan.

The Plasmodium falciparum population in Asar village, eastern Sudan, where malaria transmission is markedly seasonal, was monitored monthly over a period of 15 months. A cohort of infected patients was treated and then followed monthly throughout the dry season until the next transmission season. Parasitaemia detected by microscopy among the cohort reduced dramatically following treatment, but remained sporadic during the dry season, and reappeared following the onset of the next wet season. However between 40 and 50% of the cohort retained a persisting parasitaemia detectable by PCR throughout the dry season. These parasites were genetically complex, consisting of multiple clones with a large repertoire of alleles of the studied genes. While the number of clones per host dropped significantly following treatment of acute cases during the transmission season, drug treated people nevertheless maintained an average of one clone throughout the dry season. Allele frequencies of MSP-1, MSP-2 and GLURP showed slight, statistically insignificant, fluctuations between the dry and wet seasons. A higher frequency of inbreeding was estimated among the parasites that survived the dry season compared to the wet season

Correlation between parasite and gametocyte densities across seasons.

<p>The correlation between gametocyte and parasite densities varied across the seasons (i.e. there is a season by parasite density interaction). During the pre-clinical period, a strong and positive correlation was observed. This suggests that a larger proportion of total parasites are gametocytes during the pre-clinical season, compared to the other 3 seasons. Points represent raw data; lines represent the best-fit between values of log₁₀ parasite and gametocytes densities as classified by season. Arbitrary numbers are used to present gametocyte and total parasite densities, denoted as blood_RNA and blood_DNA, to account for sample processing differences that might result in the appearance that some samples contain more gametocytes than total parasites.</p