Estimates of the infectious reservoir of Plasmodium falciparum malaria in The Gambia and in Tanzania

Drakeley, Chris; Akim, N. I. J.; Sauerwein, Robert W.; Greenwood, Brian; Targett, G. A. T.

doi:10.1016/s0035-9203(00)90056-7

Cited by 95 publications

(87 citation statements)

References 23 publications

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“…Subsequent fertilization of gametes and development into sporozoites within the mosquito makes it infectious to another human. The human infectious reservoir is defined as the proportion of a population capable of successfully infecting mosquitoes (Drakeley et al 2000). Gametocyte carriage and successful transmission from human to mosquito is influenced by several factors including age , gametocyte density Schneider et al 2007;Ouédraogo et al 2009), gametocyte sex ratio (Robert et al 1996b;Mitri et al 2009), antimalarial drug treatment (Buckling et al 1999;Robert et al 2000;Sowunmi et al 2004), and host immunity (Fig.…”

Section: Determinants Of Infectiousnessmentioning

confidence: 99%

Biology of Malaria Transmission

Meibalan

Marti

2016

Cold Spring Harb Perspect Med

115

125

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Understanding transmission biology at an individual level is a key component of intervention strategies that target the spread of malaria parasites from human to mosquito. Gametocytes are specialized sexual stages of the malaria parasite life cycle developed during evolution to achieve crucial steps in transmission. As sexual differentiation and transmission are tightly linked, a deeper understanding of molecular and cellular events defining this relationship is essential to combat malaria. Recent advances in the field are gradually revealing mechanisms underlying sexual commitment, gametocyte sequestration, and dynamics of transmissible stages; however, key questions on fundamental gametocyte biology still remain. Moreover, species-specific variation between Plasmodium falciparum and Plasmodium vivax transmission dynamics pose another significant challenge for worldwide malaria elimination efforts. Here, we review the biology of transmission stages, highlighting numerous factors influencing development and dynamics of gametocytes within the host and determinants of human infectiousness. C urrent measures for malaria elimination have been inspired by the Global Malaria Eradication Program (GMEP), which operated under the World Health Organization (WHO) between 1955 and 1969. The strategy of GMEP was largely based on dichlorodiphenyltrichloroethane (DDT)-based indoor residual spraying (DDT-IRS) complemented with mass drug administration (Pampana 1969). Although GMEP was able to eliminate malaria from many regions of the world, it was eventually abandoned because of technical challenges, increasing spread of both insecticide resistance and drug-resistant parasite strains, and lack of continuous political support (Najera et al. 2011 ual parasites and early transmission stages, whereas mature infectious transmission stages are unaffected. To block transmission, ACT is often combined with the only transmissionblocking drug on the market, Primaquine. However, recent emergence of artemisinin resistance in Southeast Asia asks for urgent evaluation of alternative treatment strategies (Noedl et al. 2008;Dondorp et al. 2009;Mbengue et al. 2015;Straimer et al. 2015).Of the five Plasmodium species known to cause malaria in humans, Plasmodium falciparum is lethal and responsible for severe disease pathology and the majority of deaths due to malaria, especially in sub-Saharan Africa. Plasmodium vivax typically causes milder infections than P. falciparum but has a much greater geographical distribution (Gething et al. 2012). The clinical symptoms of malaria are largely a result of the replication of asexual stages in human blood, but transmission to mosquitoes is only achieved through the development of sexual stages, termed gametocytes. To abrogate transmission of P. falciparum, we must be able to clear asexual and sexual stages from the human host, eventually rendering an individual noninfectious to mosquitoes. However, in the case of P. vivax, elimination is highly challenging because of the relapse of dormant liver-stage h...

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Section: Determinants Of Infectiousnessmentioning

confidence: 99%

Biology of Malaria Transmission

Meibalan

Marti

2016

Cold Spring Harb Perspect Med

115

125

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“…Some indices have been defined, including the proportion of humans with malaria transmission stages, gametocytes in their peripheral blood, the proportion of infectious individuals, and the proportion of mosquitoes that have become infected after feeding. [11][12][13][14][15] Often, these studies were restricted to microscopically detected gametocyte carriers, even though it has been repeatedly shown that submicroscopic gametocyte densities may result in mosquito infection. 16,17 Although microscopically detectable gametocyte densities are more likely to result in mosquito infections compared with submicroscopic gametocyte densities, the contribution of submicroscopic gametocyte carriers to the total infectious reservoir may be considerable 18 and can only be determined in xenodiagnostic surveys where individuals are recruited for feeding experiments, regardless of their parasitemic status.…”

Section: Introductionmentioning

confidence: 99%

Infectiousness of the Human Population to Anopheles arabiensis by Direct Skin Feeding in an Area Hypoendemic for Malaria in Senegal

Gaye¹,

Bousema²,

Gadiaga³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Abstract. Direct skin feeding experiments are sensitive assays to determine human infectiousness to mosquitoes but are rarely used in malaria epidemiological surveys. We determined the infectiousness of inhabitants of a malaria hypoendemic area in Senegal. Gametocyte prevalence by microscopy was 13.5% (26 of 192). Of all individuals who were gametocyte positive, 44.4% (11 of 25) infected 1 Anopheles arabiensis mosquito and 10.8% (54 of 500) of mosquitoes became infected. Of all individuals who were gametocyte negative by microscopy, 4.3% (7 of 162) infected 1 mosquito and 0.4% (12 of 3240) of mosquitoes became infected. The 18.2% (12 of 66) of all mosquito infections was a result of submicroscopic gametocyte carriage and two individuals without asexual parasites or gametocytes by microscopy were infectious to mosquitoes. When infectivity and local demography was taken into account, children 5-14 years of age contributed 50.8% of the human infectious reservoir for malaria. Adults and submicroscopic gametocyte carriers may contribute considerably to onward malaria transmission in our setting.

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“…Age-pattern of infectivity. Field estimates of the relative contribution to the infectious reservoir by different age groups have been made for settings in Liberia, 9 The Gambia, 8 Tanzania, 8 western Kenya, 20 Papua New Guinea, 21 and Cameroon. 22 The estimates from Africa are based on feeding of insectary An.…”

Section: Methodsmentioning

confidence: 99%

“…There is a general decrease with age in infectiousness but even highly immune hosts contribute to the infectious reservoir. 8,9 Community effects of vaccines or of other interventions targeting the human host (herd immunity) result either directly or indirectly from changes in infectivity. To understand these, mathematical models are needed.…”

Section: Introductionmentioning

confidence: 99%

Relationships Between Host Infectivity to Mosquitoes and Asexual Parasite Density in Plasmodium Falciparum

Ross

Killeen

Smith

2006

The American Journal of Tropical Medicine and Hygiene

101

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Abstract. We describe a statistical model for the relationship between asexual parasite densities of Plasmodium falciparum and the infectivity of the host to mosquitoes. The model takes into account the delay between asexual parasitemia and infectivity resulting from the time course of gametocytemia. It also allows for the need for the blood meal to contain gametocytes of both sexes if infection is to take place. We show that by fitting this model to data from malariatherapy patients it can explain observed patterns of infectiousness of the human host and is consistent with distributions of gametocyte densities in malariatherapy patients. By integrating this model into an individual-based simulation of human populations exposed to endemic P. falciparum transmission, we are able to predict the contributions of different host age groups to the infectious reservoir. Comparison of model predictions with published estimates of this quantity confirms that infected adults hosts are likely to make a significant contribution to the reservoir of transmission, and points to the need for improved population-based estimates of this age-dependence in infectivity of humans in endemic areas.

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Estimates of the infectious reservoir of Plasmodium falciparum malaria in The Gambia and in Tanzania

Cited by 95 publications

References 23 publications

Biology of Malaria Transmission

Biology of Malaria Transmission

Infectiousness of the Human Population to Anopheles arabiensis by Direct Skin Feeding in an Area Hypoendemic for Malaria in Senegal

Relationships Between Host Infectivity to Mosquitoes and Asexual Parasite Density in Plasmodium Falciparum

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