Infectiousness Of Gametocytes Research Articles

Mosquito Feeding Assays to Determine the Infectiousness of Naturally Infected Plasmodium falciparum Gametocyte Carriers

IntroductionIn the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes.MethodsWe compared two commonly used mosquito feeding assay procedures: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum.Results930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94–2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p<0.0001). Replacing the plasma of the gametocyte donor with malaria naïve control serum resulted in higher mosquito infection rates compared to own plasma (OR 1.92, 95% CI 1.68–2.19) while the infectiousness of gametocytes may be reduced during the replacement procedure (OR 0.60, 95% CI 0.52–0.70).ConclusionsDespite a higher efficiency of direct skin feeding assays, membrane feeding assays appear suitable tools to compare the infectiousness between individuals and to evaluate transmission-reducing interventions. Several aspects of membrane feeding procedures currently lack standardization; this variability makes comparisons between laboratories challenging and should be addressed to facilitate future testing of transmission-reducing interventions.

Chloroquine/Sulphadoxine-Pyrimethamine for Gambian Children with Malaria: Transmission to Mosquitoes of Multidrug-Resistant Plasmodium falciparum

Objectives:In the Gambia, chloroquine (CQ) plus sulphadoxine-pyrimethamine (SP) is the first-line antimalarial treatment. Plasmodium falciparum parasites carrying mutations associated with resistance to each of these drugs were present in 2001 but did not cause a significant loss of therapeutic efficacy among children receiving the combination CQ/SP. We measured their effect on parasite transmission to Anopheles gambiae mosquitoes.Design:We conducted a single-blind, randomised, controlled trial with follow-up over 28 d. Mosquito feeding experiments were carried out 7, 10, or 14 d after treatment.Setting:The study took place in the town of Farafenni and surrounding villages in the Gambia.Participants:Participants were 500 children aged 6 mo to 10 y with uncomplicated P. falciparum malaria. Interventions:Children were randomised to receive CQ, SP, or CQ/SP.Outcome Measures:Outcomes related to transmission were determined, including posttreatment gametocyte prevalence and density. Infectiousness was assessed by membrane-feeding A. gambiae mosquitoes with blood from 70 gametocyte-positive patients. Mutations at seven loci in four genes associated with drug resistance were measured pre- and posttreatment and in the midguts of infected mosquitoes.Results:After SP treatment, the infectiousness of gametocytes was delayed, compared to the other two treatment groups, despite comparable gametocyte densities. Among bloodmeal gametocytes and the midguts of infected mosquitoes, the presence of the four-locus multidrug-resistant haplotype TYRG (consisting of mutations pfcrt-76T, pfmdr1-86Y, pfdhfr-59R, and pfdhps-437G) was associated with significantly higher oocyst burdens after treatment with the combination CQ/SP.Conclusions:Parasites with a multidrug-resistant genotype had a substantial transmission advantage after CQ/SP treatment but did not have a significant impact on in vivo efficacy of this drug combination. Protocols that include measuring transmission endpoints as well as therapeutic outcomes may be a useful strategy when monitoring the evolution of drug resistance in malaria parasites in vivo.

Susceptibility and Resistance of Avian and Mosquito Hosts to Strains of Plasmodium relictum Isolated from Pigeons*

SYNOPSIS. Two strains (1B and 1P) of Plasmodium relictum isolated from pigeons could be easily passed serially in pigeons by transfer of infected blood. What appeared at first to be a qualitative difference between the infectiousness of gametocytes of strain 1P in pigeons and of gametocytes of the strain after being adapted to canaries (1P1) was found to be only a quantitative difference in their infectivity for mosquitoes. Earlier work had indicated that gametocytes of strain 1P were noninfectious for mosquitoes. The experiments reported here show that Culex tarsalis is highly susceptible to gametocytes of both strains 1B and1P and that Culex pipiens is slightly susceptible to gametocytes of strain 1P.The susceptibility of 72 pigeons (belonging to 24 varieties, plus mongrels and 3 species hybrids) to sporozoites of strain 1P1 was tested; only 5 transient infections lasting no more than two days and 3 subpatent infections were obtained. Similar results were obtained with sporozoites of strain 1B.The two strains are similar in both mosquito and avian hosts except that 1B is more highly infectious for C. pipiens and C. tarsalis than 1P. There is evidence that one or both of these strains may be Plasmodium relictum matutinum, Huff(7). A proposed hypothesis indicates that (1) various species of mosquitoes have different susceptibilities, (2) various species of avian hosts are infectious to different degrees, and (3) that the probability of a mosquito of a given species being infected from a given species of parasite may be expressed by the degree of overlap between the normal curves of susceptibility of the mosquito and infectiousness of the gametocytes in the pertinent avian host. The susceptibilities of pigeons to sporozoites of the two strains of parasites and of mosquitoes to gametocytes produced in pigeons are so low that it can be questioned whether these strains could persist in nature without the presence of other avian hosts on the one hand possessing greater susceptibility than the pigeon to sporozoites and on the other hand contributing more to the infectiousness of the gametocytes than the pigeon does.

Observations on the infectiousness of gametocytes in hyperendemic malaria

1. (1) There is a correlation between the probability of a mosquito's becoming infected and the gametocyte density of the carrier, when densities are broadly grouped. 2. (2) A small series of experiments in the hyperendemic zone of S. W. Nigeria are reported in which A. gambiae gambiae were allowed to feed on children carrying different densities of P. falciparum gametocytes. 3. (3) In the community from which these subjects came the average density of gametocytes was low, approximately 5 6 of all gametocyte carriers showing less than 100 per c.mm., and 1 6 more than 100 per c.mm. 4. (4) Of mosquitoes feeding once on the first group (less than 100 gametocytes per c.mm.) 5 per cent. could become infected if they survived long enough for completion of the extrinsic cycle, while of mosquitoes feeding on the second group (more than 100 per c.mm.) 50 per cent. could become infected. Other workers have found a higher proportion infected in the first group. 5. (5) These figures are used in a hypothetical example to calculate the proportion of all A. gambiae feeding on the population at one moment which could become infected.

Changes in the Infectiousness of Gametocytes During the Course of Plasmodium Gallinaceum Infections

Changes in the Infectiousness of Gametocytes During the Course of Plasmodium Gallinaceum Infections