Monitoring Chloroquine Resistance Using Plasmodium Falciparum Parasites Isolated From Wild Mosquitoes in Tanzania

Temu, Emmanuel A.; Kimani, Issac; Tuno, Nabuko; Kawada, Hitoshi; Minjas, J.N.; Takagi, Masahiro

doi:10.4269/ajtmh.2006.75.1182

Cited by 22 publications

(25 citation statements)

References 33 publications

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“…The prevalence of mutant alleles of both Pfcrt and Pfmdr1 decreased from 64.5 to 16% and 46.6 to 2.7%, respectively. By contrast, isolates with wild-type alleles of both Pfcrt and Pfmdr1 increased significantly [59]. These findings are consistent with the loss of CQ mutants following withdrawal of the drug, and a subsequent increase of CQ-susceptible parasites.…”

Section: Chloroquinesupporting

confidence: 82%

Impaired fitness of drug-resistant malaria parasites: evidence and implication on drug-deployment policies

Babiker

Hastings

Swedberg

2009

Expert Review of Anti-infective Therapy

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Malaria, a leading parasitic disease, inflicts an enormous toll on human lives and is caused by protozoal parasites belonging to the genus Plasmodium. Antimalarial drugs targeting essential biochemical processes in the parasite are the primary resources for management and control. However, the parasite has established mutations, substantially reducing the efficacy of these drugs. First-line therapy is faced the with the consistent evolution of drug-resistant genotypes carrying these mutations. However, drug-resistant genotypes are likely to be less fit than the wild-type, suggesting that they might disappear by reducing the volume of drug pressure. A substantial body of epidemiological evidence confirmed that the frequency of resistant genotypes wanes when active drug selection declines. Drug selection on the parasite genome that removes genetic variation in the vicinity of drug-resistant genes (hitch-hiking) is common among resistant parasites in the field. This can further disadvantage drug-resistant strains and limit their variability in the face of a mounting immune response. Attempts to provide unequivocal evidence for the fitness cost of drug resistance have monitored the outcomes of laboratory competition experiments of deliberate mixtures of sensitive and resistant strains, in the absence of drug pressure, using isogenic clones produced either by drug selection or gene manipulation. Some of these experiments provided inconclusive results, but they all suggested reduced fitness of drug-resistant clones in the absence of drug pressure. In addition, biochemical analyses provided clearer information demonstrating that the mutation of some antimalarial-targeted enzymes lowers their activity compared with the wild-type enzyme. Here, we review current evidences for the disadvantage of drug-resistance mutations, and discuss some strategies of drug deployment to maximize the cost of resistance and limit its spread.

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Section: Chloroquinesupporting

confidence: 82%

Impaired fitness of drug-resistant malaria parasites: evidence and implication on drug-deployment policies

Babiker

Hastings

Swedberg

2009

Expert Review of Anti-infective Therapy

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“…arabiensis . Nonetheless, in a Tanzanian study by Temu et al [36], An. arabiensis appeared to consistently carry a lower proportion of PfCRT 76 T mutants than both An.…”

Section: Discussionmentioning

confidence: 99%

Selection for chloroquine-sensitive Plasmodium falciparum by wild Anopheles arabiensis in Southern Zambia

Mharakurwa

Sialumano²,

Liu

et al. 2013

Malar J

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BackgroundThe emergence of parasite drug resistance, especially Plasmodium falciparum, persists as a major obstacle for malaria control and elimination. To develop effective public health containment strategies, a clear understanding of factors that govern the emergence and spread of resistant parasites in the field is important. The current study documents selection for chloroquine-sensitive malaria parasites by wild Anopheles arabiensis in southern Zambia.MethodsIn a 2,000-sq km region, mosquitoes were collected from human sleeping rooms using pyrethrum spray catches during the 2006 malaria transmission season. After morphological examination and molecular confirmation, vector mosquitoes were dissected to separate head and thorax from the abdominal section, followed by PCR screening for P. falciparum infection. Human residents of all ages were tested for P. falciparum parasitaemia by microscopy and PCR. Plasmodium falciparum infections were genotyped at the chloroquine resistance-conferring amino acid codon 76 of the PfCRT gene, using PCR and restriction enzyme digestion.ResultsIn the human population there was nearly 90% prevalence of the chloroquine-resistant PfCRT K76T mutant, with no significant differences in polymorphism among smear-positive and smear-negative (submicroscopic) infections (p = 0.323, n = 128). However, infections in both abdominal and salivary gland phases of the An. arabiensis vector exhibited wild type K76-bearing parasites with up to 9X higher odds (OR (95% CI): 9 (3.7-20.2), p < 0.0005, n = 125), despite having been acquired from humans within a few weeks.ConclusionsAnopheles arabiensis selects for wild-type K76-bearing P. falciparum during both abdominal and salivary gland phases of parasite development. The rapid vectorial selection, also recently seen with antifolate resistance, is evidence for parasite fitness cost in the mosquito, and may underpin regional heterogeneity in the emergence, spread and waning of drug resistance. Understanding the nature and direction of vector selection could be instrumental for rational curtailment of the spread of drug resistance in integrated malaria control and elimination programmes.

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“…Samples used in this study were collected from households assigned to the control and hygiene intervention cohorts during the baseline visits that occurred from March-May (rainy season) 2010, and from the same households during the first follow-up visit after intervention, which occurred from September-October (dry season) 2010. 16 These households were unique from those previously described. 17,18 Households were chosen for this study by randomly selecting from household clusters in the larger, behavioral intervention trial.…”

Section: Methodsmentioning

confidence: 99%

Quantification of Human Norovirus GII on Hands of Mothers with Children Under the Age of Five Years in Bagamoyo, Tanzania

Mattioli¹,

Davis²,

Mrisho³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Human noroviruses are the most common cause of viral gastroenteritis worldwide and one of the leading causes of viral diarrhea in children under the age of 5 years. Hands have been shown to play an important role in norovirus transmission. Norovirus outbreaks tend to exhibit strong seasonality, most often occurring during cold, dry months, but recently have also been documented during hot, dry winter months in the southern hemisphere. Other research suggests that rainfall is an important factor in norovirus outbreaks. This study examines the prevalence and concentration of human norovirus GII on the hands of mothers in Bagamoyo, Tanzania, during the rainy and dry seasons. Norovirus GII was detected in approximately 5% of hand rinse samples during both the rainy and dry seasons. Fecal indicator bacteria levels, Escherichia coli and enterococci, in hand rinse samples were not associated with norovirus hand contamination. Turbidity of the hand rinses was found to be associated with norovirus presence on mothers' hands; however, this relationship was only observed during the rainy season. The results suggest mothers' hands serve as a source of norovirus exposure for young children in Tanzanian households, and further work is needed to determine better indicators of norovirus contamination in these environments.

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Monitoring Chloroquine Resistance Using Plasmodium Falciparum Parasites Isolated From Wild Mosquitoes in Tanzania

Cited by 22 publications

References 33 publications

Impaired fitness of drug-resistant malaria parasites: evidence and implication on drug-deployment policies

Impaired fitness of drug-resistant malaria parasites: evidence and implication on drug-deployment policies

Selection for chloroquine-sensitive Plasmodium falciparum by wild Anopheles arabiensis in Southern Zambia

Quantification of Human Norovirus GII on Hands of Mothers with Children Under the Age of Five Years in Bagamoyo, Tanzania

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