RTS,S/AS02 and the quest of the Holy Grail

High-profile programs under the WHO/Roll Back Malaria initiative, in addition to unravelling the human and malaria parasite genomes, have ensured that malaria vaccine research and development are enjoying an unprecedented boom. So far, the development of a vaccine against such a complex parasite has been elusive. Recently, there have also been concerns that imperfect vaccines could encourage the selection of more virulent parasite strains [1]. However, there is compelling evidence that, if an effective malaria vaccine was developed, it would prove to be protective because several studies have shown that: (1) immunity to malaria can develop of multiple Plasmodium infection; and (2) exposure to bites from irradiated Anopheles infected with Plasmodium falciparum can confer protection against infection for up to 10 months. Based on these findings, effector T-cell vaccines that rate pre-erythrocytic stages of the parasite in infected hepatocytes have been developed

Rapid Detection of Leishmania infantum Infection in Dogs: Comparative Study Using an Immunochromatographic Dipstick Test, Enzyme-Linked Immunosorbent Assay, and PCR

Current zoonotic visceral leishmaniasis (ZVL) control programs in Brazil include the culling of Leishmania infantum-infected reservoir dogs, a strategy that has failed to prevent a rise of canine and human ZVL cases over the past decade. One of the main reasons this strategy has failed is because of a long delay between sample collection, sample analysis, and control implementation. A rapid, sensitive, and specific diagnostic tool would be highly desirable, because it would allow control interventions to be implemented in situ. We compared an immunochromatographic dipstick test to enzyme-linked immunosorbent assay (ELISA) and PCR for detecting L. infantum infections in dogs from an area of ZVL endemicity in Brazil. The dipstick test was shown to have 61 to 75% specificity and 72 to 77% sensitivity, compared to 100% specificity for both ELISA and PCR and 71 to 88% and 51 to 64% sensitivity for ELISA and PCR, respectively. Of the field samples tested, 92 of 175 (53%), 65 of 175 (37%), and 47 of 175 (27%) were positive by dipstick, ELISA, and PCR, respectively. The positive and negative predictive values for the tested dipstick were 58 to 77% and 75%, respectively. Efforts should be made to develop a more specific dipstick test for diagnosis of leishmaniasis, because they may ultimately prove more cost-effective than currently used diagnostic tests when used in mass-screening surveys

Evaluation of PCR as a diagnostic mass-screening tool to detect Leishmania (Viannia) spp. in domestic dogs (Canis familiaris).

Several studies have suggested that the PCR could be used in epidemiological mass-screening surveys to detect Leishmania (Viannia) spp. infection in human and animal hosts. Dogs from an area of Leishmania braziliensis and Leishmania peruviana endemicity were screened for American cutaneous leishmaniasis (ACL) infection by established PCR-based and enzyme-linked immunosorbent antibody test (ELISA) protocols. PCR detected Leishmania (Viannia) infection in a total of 90 of 1,066 (8.4%) dogs: 32 of 368 (8.7%), 65 of 769 (8.5%), and 7 of 42 (16.7%) dogs were PCR positive by testing of whole blood, buffy coat, and bone marrow aspirates, respectively. ELISA detected infection in 221 of 1,059 (20.9%) tested dogs. The high prevalence of Leishmania (Viannia) detected by PCR and ELISA in both asymptomatic (7.5 and 19.2%, respectively) and symptomatic (32 and 62.5%, respectively) dogs is further circumstantial evidence for their suspected role as reservoir hosts of ACL. However, the low sensitivity of PCR (31%) compared to ELISA (81%) indicates that PCR cannot be used for mass screening of samples in ACL epidemiological studies. Unless more-sensitive PCR protocols were to be developed, its use should be restricted to the diagnosis of active (canine and human) cases and to the parasitological monitoring of patients after chemotherapy

Topical insecticide treatments to protect dogs from sand fly vectors of leishmaniasis.

We compared the susceptibility of sand fly vectors to four topical insecticide treatments applied to domestic dogs, a reservoir of human leishmaniasis. Dogs were exposed to sand flies pretreatment and at 1 week, 1 month, and 2 months posttreatment. Sand fly bloodfeeding and survival rate of both fed and unfed flies were significantly reduced by the permethrin, deltamethrin, and fenthion treatments, but diazinon had no effect. The survival rate of bloodfed sand flies was reduced by up to 86% with deltamethrin collars. The antifeeding effect suggests that deltamethrin collars may be recommended to dog owners to protect their pets from sandfly- borne diseases. The combined effects on sand fly feeding and survival indicate that epidemiologic, community-based trials are warranted to test whether deltamethrin collars could reduce the incidence of canine and, hence, human leishmaniasis

Risk Factors for Anthroponotic Cutaneous Leishmaniasis at the Household Level in Kabul, Afghanistan

Cutaneous leishmaniasis is a vector-borne protozoan disease that is characterized by cutaneous lesions which develop at the site of the insect bite. Lesions can vary in severity, clinical appearance, and time to cure; in a proportion of patients lesions can become chronic, leading to disfiguring mucosal leishmaniasis or leishmaniasis recidvans. Albeit not fatal, cutaneous leishmaniasis can have a significant social impact as it may lead to severe stigmatisation of affected individuals when lesions or scars occur on the face and exposed extremeties. Over the last 10–20 years there has been an increase in the number of leishmaniasis cases reported in South Asia, particularly in Afghanistan. Little is known about the household-level risk factors for infection and disease. Here we confirm previous reports that had shown the association of cutaneous leishmaniasis with age and clustering of cases at the household-level. Additionally, we show that risk of cutaneous leishmaniasis is associated with household construction (i.e. brick walls) and design (i.e. proportion of windows with screens)

Efficacy of Thermotherapy to Treat Cutaneous Leishmaniasis Caused by Leishmania tropica in Kabul, Afghanistan: A Randomized, Controlled Trial

BACKGROUND: Pentavalent antimony is the agent recommended for treatment of cutaneous leishmaniasis (CL). Its use is problematic, because it is expensive and because of the potential for drug-associated adverse effects during a lengthy and painful treatment course. METHODS: We tested the efficacy of thermotherapy for the treatment of CL due to Leishmania tropica in a randomized, controlled trial in Kabul, Afghanistan. We enrolled 401 patients with a single CL lesion and administered thermotherapy using radio-frequency waves (1 treatment of ≥1 consecutive application at 50°C for 30 s) or sodium stibogluconate (SSG), administered either intralesionally (a total of 5 injections of 25 mL every 57 days, depending on lesion size) or intramuscularly (20 mg/kg daily for 21 days). RESULTS: Cure, defined as complete reepithelialization at 100 days after treatment initiation, was observed in 75 (69.4%) of 108 patients who received thermotherapy, 70 (75.3%) of 93 patients who received intralesional SSG, and 26 (44.8%) of 58 patients who received intramuscular SSG. The OR for cure with thermotherapy was 2.80 (95% confidence interval [CI], 1.455.41), compared with intramuscular SSG treatment (P = .002). No statistically significant difference was observed in the odds of cure in comparison of intralesional SSG and thermotherapy treatments. The OR for cure with intralesional SSG treatment was 3.75 (95% CI, 1.867.54), compared with intramuscular SSG treatment (P 100 days, respectively; P = .003). CONCLUSIONS: Thermotherapy is an effective, comparatively well-tolerated, and rapid treatment for CL, and it should be considered as an alternative to antimony treatment

Leishmania (Viannia) spp. dissemination and tissue tropism in naturally infected dogs (Canis familiaris).

First evidence is presented for Leishmania (Viannia) spp. dissemination and tissue tropism in the domestic dog. Using PCR and histology, parasites were detected in the conjunctiva, lung, lymph nodes and ovaries of 2 naturally infected Peruvian dogs. The detection of parasites in the blood indicates that parasite dissemination to those organs may have been haematogenous

Designing a Story Database for Use in Automatic Story Generation

In this paper we propose a model for the representation of stories in a story database. The use of such a database will enable computational story generation systems to learn from previous stories and associated user feedback, in order to create believable stories with dramatic plots that invoke an emotional response from users. Some of the distinguishing characteristics of our proposal are the inclusion of what we call ‘narratological concepts’ and user feedback in the story database