Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes

Componentes não carcaça de novilhos de corte submetidos à castração cirúrgica ou imunológica

Objetivou-se avaliar as características dos componentes do corpo vazio que não integram a carcaça de novilhos castrados cirurgicamente ou imunologicamente. Foram utilizados 48 bezerros Aberdeen Angus, monitorados a partir de idade média inicial de seis meses e peso médio inicial de 160 kg. Os animais foram distribuídos nos seguintes tratamentos: castrados cirurgicamente ao nascimento; castrados cirurgicamente à desmama; imunocastrados com três doses de vacina (6º, 9º e 14º meses de idade dos animais) e imunocastrados com quatro doses (6º, 7º, 10º e 15º meses de idade dos animais). O delineamento experimental foi o inteiramente casualizado. Durante o abate, todos os componentes internos e externos do corpo do animal foram separados e pesados individualmente. O total de órgãos internos expressos em percentual do peso de corpo vazio diferiu entre os dois protocolos de imunocastração, com superioridade quando aplicou-se quatro doses (3,61 vs. 3,39 kg). Novilhos castrados ao nascer depositaram mais gordura cardíaca, renal e pélvica, e gordura do trato gastrintestinal que imunocastrados com três doses, independentemente da forma como foi expressa. A castração cirúrgica ao nascimento promove maior deposição de gordura visceral, em novilhos abatidos em idade jovem, em relação à imunocastração com dosagem definitiva com nove meses de idade

Efeito heterótico sobre o desempenho e medidas corporais de novilhos confinados

The objective of this study was to evaluate the heterotic effect on performance and body measurements of Charolais (Ch) and Nellore (Ne) steers and crossbreeds from the fifth (21/32Ch 11/32Ne; 21/32Ne 11/32Ch) e sixth (43/64Ch 21/64Ne; 43/64Ne 21/64Ch) generation, feedlot finished. For initial weight, the heterotic effect was 45.9 and 39.1 kg in the fifth and sixth generation, and 41.6 and 38.1 kg for the fi nal weight, respectively, in the same order. For the average daily gain, the heterotic effect was significant in the fifth generation (0.18 kg). Heterotic effect was observed in the initial rump height in the fifth generation (6.14 cm), and in the fifth and sixth generation on final rump height, with values of 5.57 and 4.75 cm, respectively, taking into account the heterotic effect. In relation to withers height, the heterotic effect was significant on fifth and sixth generations for the initial measurement, 7.36 and 7.12 cm, respectively, and finally, 5.19 and 4.33 cm, in the same order, and on withers growth on sixth generation (-2,79 cm). For the initial length, the heterotic effect was 7.60 and 5.72 in the fifth and sixth generations, and negative in fifth (-5.29 cm) and sixth (-3.75 cm) generations for the length of growth. For thoracic perimeter, on initial measurement heterotic effect was observed on both generations, being 10.2 cm on the fifth and 8.05 on the sixth generation, however for the final measurement the heterotic effect was significant only on the fifth generation (6.00 cm). The initial measurement with the highest correlation with the average daily gain was the length (r=0.47; p=0.0007), and with the final weight was the thoracic perimeter (r=0.89; p<0,0001).Objetivou-se avaliar o efeito heterótico sobre o desempenho e medidas corporais de novilhos do cruzamento entre as raças Charolês (Ch) e Nelore (Ne) e cruzados entre essas raças de quinta (21/32Ch 11/32Ne; 21/32Ne 11/32Ch) e sexta (43/64Ch 21/64Ne; 43/64Ne 21/64Ch) gerações, terminados em confinamento. Para o peso inicial, o efeito heterótico foi de 45,9 e 39,1 kg na quinta e sexta gerações, respectivamente, e de 41,6 e 38,1 kg para o peso final, na quinta e sexta gerações, citados na mesma ordem. Para o ganho médio diário, o efeito heterótico foi significativo na quinta geração do cruzamento (0,18 kg). Houve efeito heterótico para a altura de cernelha inicial na quinta geração (6,14 cm), e na quinta e sexta gerações na medida final de altura de cernelha, com valores de 5,57 e 4,75 cm, respectivamente. Com relação à altura de garupa, o efeito heterótico foi significativo na quinta e sexta gerações para as medidas iniciais, 7,36 e 7,12 cm e final, 5,19 e 4,33 cm, respectivamente, citados na mesma ordem, e para ganho em altura de garupa na sexta geração (-2,79 cm). Para comprimento inicial, o efeito heterótico foi, respectivamente, de 7,60 e 5,72 cm na quinta e sexta gerações, e negativo na quinta (-5,29 cm) e na sexta (-3,75 cm) gerações para o ganho em comprimento. Para as mensurações do perímetro torácico, na medida inicial houve efeito heterótico em ambas as gerações avaliadas, sendo de 10,2 cm na quinta geração e 8,05 cm na sexta geração, ao passo que para a medida fi nal o efeito heterótico foi significativo apenas na quinta geração (6,00 cm). A medida inicial melhor correlacionada ao ganho médio diário de peso foi o comprimento, com r=0,47 e p=0,0007, e com o peso final o perímetro torácico (r=0,89; p<0,0001)

Detection of Plasmodium falciparum in laboratory-reared and naturally infected wild mosquitoes using near-infrared spectroscopy.

There is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes

A non-destructive sugar-feeding assay for parasite detection and estimating the extrinsic incubation period of Plasmodium falciparum in individual mosquito vectors

Despite its epidemiological importance, the time Plasmodium parasites take to achieve development in the vector mosquito (the extrinsic incubation period, EIP) remains poorly characterized. A novel non-destructive assay designed to estimate EIP in single mosquitoes, and more broadly to study Plasmodium–Anopheles vectors interactions, is presented. The assay uses small pieces of cotton wool soaked in sugar solution to collect malaria sporozoites from individual mosquitoes during sugar feeding to monitor infection status over time. This technique has been tested across four natural malaria mosquito species of Africa and Asia, infected with Plasmodium falciparum (six field isolates from gametocyte-infected patients in Burkina Faso and the NF54 strain) and across a range of temperatures relevant to malaria transmission in field conditions. Monitoring individual infectious mosquitoes was feasible. The estimated median EIP of P. falciparum at 27 °C was 11 to 14 days depending on mosquito species and parasite isolate. Long-term individual tracking revealed that sporozoites transfer onto cotton wool can occur at least until day 40 post-infection. Short individual EIP were associated with short mosquito lifespan. Correlations between mosquito/parasite traits often reveal trade-offs and constraints and have important implications for understanding the evolution of parasite transmission strategies

Comparative assessment of An. gambiae and An. stephensi mosquitoes to determine transmission-reducing activity of antibodies against P. falciparum sexual stage antigens.

BACKGROUND: With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa. METHODS: Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An. stephensi and An. gambiae mosquitoes. RESULTS: In the absence of transmission-reducing antibodies, average numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody-mediated TRA was strongly correlated between both mosquito species, and absolute TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no significant difference between the two species. TRA estimates for IgG of naturally exposed individuals and partially effective concentrations of anti-Pfs25 mAb were higher for An. stephensi than for An. gambiae. CONCLUSION: Our findings support the use of An. stephensi in the SMFA for target prioritization. As a vaccine moves through product development, better estimates of TRA and transmission-blocking activity (TBA) may need to be obtained in epidemiologically relevant parasite-species combination