Experimental Infection of the Neotropical Malaria Vector Anopheles Darlingi by Human Patient-Derived Plasmodium Vivax in the Peruvian Amazon

Abstract

Malaria transmission from humans to mosquitoes is modulated by human host immune factors. Understanding mechanisms by which the human host response may impair parasite infectivity for mosquitoes has direct implications for the development of transmission-blocking vaccines. We hypothesized that despite a low transmission intensity of malaria in the Peruvian Amazon region of Iquitos, transmission-blocking immunity against Plasmodium vivax might be common, given an unexpectedly high proportion of asymptomatic parasitemic individuals in this region. To test this hypothesis, the ability of symptomatic P. vivax malaria patients to experimentally infect wild-caught outbred Anopheles darlingi mosquitoes was tested using the indirect membrane feeding technique. Only half (52/102) of P. vivax parasitemic patients successfully infected mosquitoes. Transmitters were more likely to have gametocytes (OR 6.35, P = 0.003), high parasitemia (OR 3.79, P = 0.024), and, in terms of basic clinical parameters, a slower pulse rate (mean +/- SD: 82.3 +/- 12.3 versus 88.7 +/- 13.5, P = 0.016) than non-transmitters. Log(10) gametocytemia and log(10) real-time reverse transcriptase Pvs25 PCR quantifying gametocytes were significantly and positively correlated with oocyst counts (correlation coefficient 0.505, R2 = 0.26, P = 0.001). These experiments are the first to establish a system of determining transmission patterns in experimental infection of outbred natural neotropical malaria vectors in the Amazon region. Patients with P. vivax inefficiently infect outbred An. darlingi mosquitoes, raising the possibility that some degree of naturally occurring transmission-blocking immunity is present on a population basis in the Peruvian Amazon, an area of low intensity of malaria transmission.

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

“…Groups were similar for age, sex, days of symptoms, and parasitemia, heart rate, respiratory rate, and hematocrit, but were significantly different for temperature, which was on average 0.6 C higher among the nontransmitters (Table 1), as seen previously. 2 Transmission association with parasitemia. Infection per parasitemia range was analyzed (Figure 1).…”

“…Of this, 6 mL of this blood was used (within 5-10 minutes) in a standard membrane feeding assay (MFA) with F1 generation Anopheles darlingi as previously described. 2 Mosquitoes were allowed to feed until engorgement for~15-30 minutes. Non-engorged mosquitoes were removed before analysis.…”

“…Although host antibodies [6][7][8] have been shown to affect parasite infectivity for mosquitoes, transmission inefficiency is still observed in malaria hypoendemic regions where presence of antibody is thought to be low. 2,9 Previous work in Sri Lanka has suggested that humoral factors associated with the malarial paroxism reduces parasite infectivity for mosquitoes. 5,10 In this study, we hypothesized that cell-mediated immunity as assessed by serum cytokines as a biomarker would influence transmission.…”

“…[1][2][3][4][5] A variety of determinants modulate transmission, including gametocyte quality, vector competence, and human innate and acquired immunity. Although host antibodies [6][7][8] have been shown to affect parasite infectivity for mosquitoes, transmission inefficiency is still observed in malaria hypoendemic regions where presence of antibody is thought to be low.…”

Retos de la entomología médica para la vigilancia en salud pública en Colombia: reflexión para el caso de malaria

“…El único denominador común es A. darlingi, y varios estudios avalan la tendencia antropofilica y la capacidad vectorial de esta especie (14)(15)(16). Esta situación se torna particularmente preocupante en las áreas limítrofes entre los países, en donde las especies son las mismas independientemente de las fronteras geográficas, pero las consideraciones sobre cuáles de éstas son vectores y las acciones de control siguen los lineamientos particulares de cada país.…”