Most intestinal parasites are cosmopolitan with the highest prevalence in the tropics and subtopics. Rural-to-urban migration rapidly increases the number of food eating places in towns and their environs. Some of these eating estabishments have poor sanitation and are overcrowded, facilitating disease transmission, especially through food-handling. Our investigations in Nairobi, therefore, were set to determine the presence of intestinal parasites in food-handlers with valid medical certificates. Direct and concentrated stool processing techniques were used. Chisquare test and ANOVA were used for data analysis. The parasites Ascaris lumbricoides, Entamoeba histolytica and Giardia lamblia were observed in certified food-handlers. Significant difference was found in parasite frequency by eating classes and gender (χ2 = 9.49, P = 0.73), (F = 1.495, P = 0.297), but not in parasite occurrence between age brackets (χ2 = 6.99, P = 0.039). The six-month medical certificate validity period may contribute significantly to the presence of intestinal parasites in certified food-handlers.
We have selected piperaquine (PQ) and lumefantrine (LM) resistant Plasmodium berghei ANKA parasite lines in mice by drug pressure. Effective doses that reduce parasitaemia by 90% (ED90) of PQ and LM against the parent line were 3.52 and 3.93 mg/kg, respectively. After drug pressure (more than 27 passages), the selected parasite lines had PQ and LM resistance indexes (I90) [ED90 of resistant line/ED90 of parent line] of 68.86 and 63.55, respectively. After growing them in the absence of drug for 10 passages and cryo-preserving them at −80 °C for at least 2 months, the resistance phenotypes remained stable. Cross-resistance studies showed that the PQ-resistant line was highly resistant to LM, while the LM-resistant line remained sensitive to PQ. Thus, if the mechanism of resistance is similar in P. berghei and Plasmodium falciparum, the use of LM (as part of Coartem®) should not select for PQ resistance.
Background: The human malaria parasite
Plasmodium falciparum has evolved complex drug evasion mechanisms to all available antimalarials. To date, the combination of amodiaquine-artesunate is among the drug of choice for treatment of uncomplicated malaria. In this combination, a short acting, artesunate is partnered with long acting, amodiaquine for which resistance may emerge rapidly especially in high transmission settings. Here, we used a rodent malaria parasite
Plasmodium berghei ANKA as a surrogate of
P. falciparum to investigate the mechanisms of amodiaquine resistance.
Methods: We used serial technique to select amodiaquine resistance by submitting the parasites to continuous amodiaquine pressure. We then employed the 4-Day Suppressive Test to monitor emergence of resistance and determine the cross-resistance profiles. Finally, we genotyped the resistant parasite by PCR amplification, sequencing and relative quantitation of mRNA transcript of targeted genes.
Results: Submission of
P. berghei ANKA to amodiaquine pressure yielded resistant parasite within thirty-six passages. The effective dosage that reduced 90% of parasitaemia (ED
90) of sensitive line and resistant line were 4.29mg/kg and 19.13mg/kg, respectively. After freezing at -80ºC for one month, the resistant parasite remained stable with an ED
90 of 18.22mg/kg. Amodiaquine resistant parasites are also resistant to chloroquine (6fold), artemether (10fold), primaquine (5fold), piperaquine (2fold) and lumefantrine (3fold). Sequence analysis of
Plasmodium berghei chloroquine resistant transporter revealed His95Pro mutation. No variation was identified in
Plasmodium berghei multidrug resistance gene-1 (Pbmdr1), Plasmodium berghei deubiquitinating enzyme-1 or
Plasmodium berghei Kelch13 domain nucleotide sequences. Amodiaquine resistance is also accompanied by high mRNA transcripts of key transporters;
Pbmdr1,
V-type/H+ pumping pyrophosphatase-2 and
sodium hydrogen ion exchanger-1 and Ca
2+/H
+ antiporter.
Conclusions: Selection of amodiaquine resistance yielded stable “multidrug-resistant’’ parasites and thus may be used to study common resistance mechanisms associated with other antimalarial drugs. Genome wide studies may elucidate other functionally important genes controlling AQ resistance in
P. berghei.
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