Predicting mosquito infection from Plasmodium falciparum gametocyte density and estimating the reservoir of infection

Transmission reduction is a key component of global efforts to control and eliminate malaria; yet, it is unclear how the density of transmission stages (gametocytes) influences infection (proportion of mosquitoes infected). Human to mosquito transmission was assessed using 171 direct mosquito feeding assays conducted in Burkina Faso and Kenya. Plasmodium falciparum infects Anopheles gambiae efficiently at low densities (4% mosquitoes at 1/µl blood), although substantially more (>200/µl) are required to increase infection further. In a site in Burkina Faso, children harbour more gametocytes than adults though the non-linear relationship between gametocyte density and mosquito infection means that (per person) they only contribute slightly more to transmission. This method can be used to determine the reservoir of infection in different endemic settings. Interventions reducing gametocyte density need to be highly effective in order to halt human–mosquito transmission, although their use can be optimised by targeting those contributing the most to transmission. DOI: http://dx.doi.org/10.7554/eLife.00626.001

[1]  J. Sattabongkot,et al.  Correlation of Pfg377 ortholog gene expression of Plasmodium vivax and mosquito infection , 2012, Tropical medicine & international health : TM & IH.

[2]  Christine Osborne,et al.  Statistical Calibration: A Review , 1991 .

[3]  A. Lensen,et al.  Plasmodium falciparum: infectivity of cultured, synchronized gametocytes to mosquitoes. , 1999, Experimental parasitology.

[4]  P. Carnevale,et al.  [The aggressiveness of Anopheles gambiae A in relation to the age and sex of the human subjects]. , 1978, Bulletin of the World Health Organization.

[5]  Petra Schneider.  Submicroscopic Plasmodium falciparum gametocytaemia and the contribution of malaria transmission. , 2006 .

[6]  F. Collins,et al.  The reservoir of Plasmodium falciparum malaria in a holoendemic area of western Kenya. , 1992, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[7]  [A Bayesian Analysis of the Linear Calibration Problem]: Response , 1981 .

[8]  R. Sinden,et al.  Progression of Plasmodium berghei through Anopheles stephensi Is Density-Dependent , 2007, PLoS pathogens.

[9]  David L Smith,et al.  Revisiting the Basic Reproductive Number for Malaria and Its Implications for Malaria Control , 2007, PLoS biology.

[10]  T. Bousema,et al.  The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso , 2010, Malaria Journal.

[11]  Gerry Killeen,et al.  Relationships between host infectivity to mosquitoes and asexual parasite density in Plasmodium falciparum. , 2006, The American journal of tropical medicine and hygiene.

[12]  David L. Smith,et al.  Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations , 2009, Malaria Journal.

[13]  R. Hayes,et al.  How many patients with a sexually transmitted infection are cured by health services? A study from Mwanza region, Tanzania , 2001, Tropical medicine & international health : TM & IH.

[14]  R. Sauerwein,et al.  Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. , 2007, The American journal of tropical medicine and hygiene.

[15]  E. Levashina,et al.  Genetic clonality of Plasmodium falciparum affects the outcome of infection in Anopheles gambiae. , 2012, International journal for parasitology.

[16]  J. Meunier,et al.  Estimation of malaria transmission from humans to mosquitoes in two neighbouring villages in south Cameroon: evaluation and comparison of several indices. , 2003, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[17]  Wes Hinsley,et al.  Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies , 2010, PLoS medicine.

[18]  R. Sinden,et al.  Measuring the blockade of malaria transmission--an analysis of the Standard Membrane Feeding Assay. , 2012, International journal for parasitology.

[19]  P. Carnevale,et al.  Etude de l'agressivité d' Anopheles gambiae A en fonction de l'âge et du sexe des appâts humains , 1978 .

[20]  R. C. Muirhead-Thomson.  The malarial infectivity of an African village population to mosquitoes (Anopheles gambiae); a random xenodiagnostic survey. , 1957, The American journal of tropical medicine and hygiene.

[21]  B. Hoadley.  A Bayesian Look at Inverse Linear Regression , 1970 .

[22]  Bradley P. Carlin,et al.  Bayesian measures of model complexity and fit , 2002 .

[23]  R. Lathe.  Phd by thesis , 1988, Nature.

[24]  M A Dowling,et al.  A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia. , 1966, Bulletin of the World Health Organization.

[25]  P. Ambroise‐Thomas,et al.  Epidemiology of Plasmodium falciparum in a rice field and a savanna area in Burkina Faso: seasonal fluctuations of gametocytaemia and malarial infectivity. , 1991, Annals of tropical medicine and parasitology.

[26]  D E EYLES,et al.  Infectivity to mosquitoes of Plasmodium falciparum as related to gametocyte density and duration of infection. , 1955, The American journal of tropical medicine and hygiene.

[27]  Teun Bousema,et al.  Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination , 2011, Clinical Microbiology Reviews.

[28]  D B Rubin,et al.  Markov chain Monte Carlo methods in biostatistics , 1996, Statistical methods in medical research.

[29]  T. Bousema,et al.  Substantial Contribution of Submicroscopical Plasmodium falciparum Gametocyte Carriage to the Infectious Reservoir in an Area of Seasonal Transmission , 2009, PloS one.

[30]  C. Drakeley,et al.  Transmission‐reducing immunity is inversely related to age in Plasmodium falciparum gametocyte carriers , 2006, Parasite immunology.

[31]  Petra Schneider,et al.  Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification. , 2004, Molecular and biochemical parasitology.

[32]  C. Drakeley,et al.  Estimates of the infectious reservoir of Plasmodium falciparum malaria in The Gambia and in Tanzania. , 2000, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[33]  Andrew Thomas,et al.  The BUGS project: Evolution, critique and future directions , 2009, Statistics in medicine.

[34]  P. Garner,et al.  Primaquine for reducing Plasmodium falciparum transmission. , 2012, The Cochrane database of systematic reviews.

[35]  N. White.  Primaquine to prevent transmission of falciparum malaria. , 2013, The Lancet. Infectious diseases.

[36]  R. May.  Togetherness among Schistosomes: its effects on the dynamics of the infection , 1977 .

[37]  J. Charlwood,et al.  Absence of relationships between selected human factors and natural infectivity of Plasmodium falciparum to mosquitoes in an area of high transmission , 1996, Parasitology.

[38]  Ogobara K. Doumbo,et al.  A Research Agenda to Underpin Malaria Eradication , 2011, PLoS medicine.

[39]  P. Ambroise‐Thomas,et al.  High human malarial infectivity to laboratory-bred Anopheles gambiae in a village in Burkina Faso. , 1993, The American journal of tropical medicine and hygiene.

[40]  C. Eisenhart,et al.  The Interpretation of Certain Regression Methods and Their Use in Biological and Industrial Research , 1939 .

[41]  T. Bousema,et al.  Can field-based mosquito feeding assays be used for evaluating transmission-blocking interventions? , 2013, Trends in parasitology.

[42]  A. Gardner,et al.  Sex ratio adjustment and kin discrimination in malaria parasites , 2008, Nature.

[43]  T. Burkot,et al.  Measurement of malarial infectivity of human populations to mosquitoes in the Madang area, Papua New Guinea , 1988, Parasitology.