Assessing key safety concerns of a Wolbachia-based strategy to control dengue transmission by Aedes mosquitoes

Mosquito-borne diseases such as dengue fever, chikungunya or malaria affect millions of people each year and control solutions are urgently needed. An international research program is currently being developed that relies on the introduction of the bacterial endosymbiont Wolbachia pipientis into Aedes aegypti to control dengue transmission. In order to prepare for open-field testing releases of Wolbachia-infected mosquitoes, an intensive social research and community engagement program was undertaken in Cairns, Northern Australia. The most common concern expressed by the diverse range of community members and stakeholders surveyed was the necessity of assuring the safety of the proposed approach for humans, animals and the environment. To address these concerns a series of safety experiments were undertaken. We report in this paper on the experimental data obtained, discuss the limitations of experimental risk assessment and focus on the necessity of including community concerns in scientific research.

Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

The present review describes recent research on the regulation by glutamate and Ca2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca2+. The lack of external Ca2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca2+-dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not act by liberating Ca2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca2+ entry into the astrocytes and consequently down-regulates a Ca2+-dependent dephosphorylation cascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during which astrocytes are known to proliferate. Possibly, glutamate liberated from developing synapses during this period may signal an increase in the phosphorylation

HIV rapid testing as a key strategy for prevention of mother-to-child transmission in Brazil

OBJECTIVE: To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS: Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS: HIV prevalence in women was 6.5% (N=1,439) in Porto Alegre and 1.3% (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS: The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.

CHEMOPROPHYLAXIS TO CONTROL LEPROSY AND THE PERSPECTIVE OF ITS IMPLEMENTATION IN BRAZIL: A PRIMER FOR NON-EPIDEMIOLOGISTS

The occurrence of leprosy has decreased in the world but the perspective of its elimination has been questioned. A proposed control measure is the use of post-exposure chemoprophylaxis (PEP) among contacts, but there are still questions about its operational aspects. In this text we discuss the evidence available in literature, explain some concepts in epidemiology commonly used in the research on this topic, analyze the appropriateness of implementing PEP in the context of Brazil, and answer a set of key questions. We argue some points: (1) the number of contacts that need to receive PEP in order to prevent one additional case of disease is not easy to be generalized from the studies; (2) areas covered by the family health program are the priority settings where PEP could be implemented; (3) there is no need for a second dose; (4) risk for drug resistance seems to be very small; (5) the usefulness of a serological test to identify a higher risk group of individuals among contacts is questionable. Given that, we recommend that, if it is decided to start PEP in Brazil, it should start on a small scale and, as new evidence can be generated in terms of feasibility, sustainability and impact, it could move up a scale, or not, for a wider intervention.

A key for identifying faecal smears to detect domestic infestations of triatomine bugs

Early detection of residual populations of domestic triatomine bugs that survive insecticide treatment is a key component of successful evaluation and vigilance for Chagas disease control. We have recently demonstrated that sheets of paper, tacked on to the walls of infested houses, can become streaked with the faeces of triatomine bugs and thus reveal thepresence of an infestation. In thispaper, wepresent a simple key to differentiate the faecal streaks of triatomine bugs from those of other domestic arthropods such as cockroaches, ticks and cimicid bedbugs.

Schistosoma mansoni: control of female fertility by the male

We have established an in vitro culture system for adult schistosomes that allows monitoring gene expression for up to more than ten days. Comparing female worms that are paired with those that have been separated, we find distinct differences, clearly documenting an influence of the male in female gene expression. In perfect coincidence with classical observations that were based on histological techniques, we find that the male particularly regulates gene expression in those tissues that are characterized by cell proliferation, e.g. the vitellaria. From these results, we hypothesize that the key target for the inductive signal that is transferred from the male to the female during pairing is the activation of a growth factor that stimulates mitotic proliferation.

Current concepts of snail control

Schistosomiasis control was impossible without effective tools. Synthetic molluscicides developed in the 1950s spearheaded community level control. Snail eradication proved impossible but repeated mollusciciding to manage natural snail populations could eliminate transmission. Escalating costs, logistical complexity, its labour-intensive nature and possible environmental effects caused some concern. The arrival of safe, effective, single-dose drugs in the 1970s offered an apparently better alternative but experience revealed the need for repeated treatments to minimise reinfection in programmes relying on drugs alone. Combining treatment with mollusciciding was more successful, but broke down if mollusciciding was withdrawn to save money. The provision of sanitation and safe water to prevent transmission is too expensive in poor rural areas where schistosomiasis is endemic; rendering ineffective public health education linked to primary health care. In the tropics, moreover, children (the key group in maintaining transmission) will always play in water. Large scale destruction of natural snail habitats remains impossibly expensive (although proper design could render many new man-made habitats unsuitable for snails). Neither biological control agents nor plant molluscicides have proved satisfactory alternatives to synthetic molluscicides. Biologists can develop effective strategies for using synthetic molluscicides in different epidemiological situations if only, like drugs, their price can be reduced.

Control of urinary schistosomiasis on Zanzibar (Unguja Island): a pilot evaluation of the educational impact of the Juma na Kichocho health booklet within primary schools

To improve health education within primary schools, the health education booklet Juma na kichocho was evaluated during a study within 5 schools using key-informant questionnaires that recorded children's knowledge and attitude (KA) towards schistosomiasis before and after daily structured-use of booklets. A total of 229 schoolchildren (114 boys : 115 girls) of between 11 and 15 years of age were interviewed and re-assessed after a working school week. Existing and putative booklet-induced changes in KA scores for schistosomiasis were compared directly against equivalent KA scores for malaria. In total 47.4% of children were already aware that schistosomiasis was a water-borne disease while only 10.5% knew of its exact aetiology; after booklet intervention these levels increased to 54.6 and 15.7%, respectively. The majority of children still failed, however, to realise that re-infection could take place soon after treatment. While a positive increase was observed for children's total KA questionnaire scores for both malaria and schistosomiasis after booklet intervention, these were not statistically significant. In the context of control, further educational efforts are needed to promote and guide behavioural change, especially in relation to reduction of environmental water contact.

Certifying achievement in the control of Chagas disease native vectors: what is a viable scenario?

As an evaluation scheme, we propose certifying for “control”, as alternative to “interruption”, of Chagas disease transmission by native vectors, to project a more achievable and measurable goal and sharing good practices through an “open online platform” rather than “formal certification” to make the key knowledge more accumulable and accessible.

Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

The role of primary care in the prevention and control of healthcare associated infections

Little research has been conducted to date on the role of primary health care (PHC) in the prevention of healthcare associated infections (HCAIs). The present article is a theoretical study of the principle of primum non nocere and aims to promote reflection on the role of PHC in HCAI prevention with emphasis on practical recommendations. The indirect and direct roles of PHC in HCAI prevention are debated in light of this guiding principle. With respect to the indirect role of PHC, we discuss the issues of hospital-centrism and ambulatory care-sensitive conditions. The article outlines a number of challenges faced by health services related to PHC’s direct role in HCAI prevention, highlights seven key components of HCAI prevention programmes within the PHC sphere and provides practical recommendations for HCAI control and prevention.


Review of semiochemicals that mediate the oviposition of mosquitoes: a possible sustainable tool for the control and monitoring of Culicidae

The choice for suitable places for female mosquitoes to lay eggs is a key-factor for the survival of immature stages (eggs and larvae). This knowledge stands out in importance concerning the control of disease vectors. The selection of a place for oviposition requires a set of chemical, visual, olfactory and tactile cues that interact with the female before laying eggs, helping the localization of adequate sites for oviposition. The present paper presents a bibliographic revision on the main aspects of semiochemicals in regard to mosquitoes' oviposition, aiding the comprehension of their mechanisms and estimation of their potential as a tool for the monitoring and control of the Culicidae.

Key factors to inoculate Botrytis cinerea in tomato plants

Studies addressing the biological control of Botrytis cinerea have been unsuccessful because of fails in inoculating tomato plants with the pathogen. With the aim of establishing a methodology for inoculation into stems, experiments were designed to assess: i. the aggressiveness of pathogen isolates; ii. the age at which tomato plants should be inoculated; iii. the susceptibility of tissues at different stem heights; iv. the need for a moist chamber after inoculation; and v. the effectiveness of gelatin regarding inoculum adhesion. Infection with an isolate from tomato plants that was previously inoculated into petioles and then re-isolated was successful. An isolate from strawberry plants was also aggressive, although less than that from tomato plants. Tomato plants close to flowering, at 65 days after sowing, and younger, middle and apical stem portions were more susceptible. There was positive correlation between lesion length and sporulation and between lesion length and broken stems. Lesion length and the percentage of sporulation sites were reduced by using a moist chamber and were not affected by adding gelatin to the inoculum suspension. This methodology has been adopted in studies of B. cinerea in tomato plants showing reproducible results. The obtained results may assist researchers who study the gray mold.

Heparan sulfate and control of cell division: adhesion and proliferation of mutant CHO-745 cells lacking xylosyl transferase

We have examined the role of cell surface glycosaminoglycans in cell division: adhesion and proliferation of Chinese hamster ovary (CHO) cells. We used both wild-type (CHO-K1) cells and a mutant (CHO-745) which is deficient in the synthesis of proteoglycans due to lack of activity of xylosyl transferase. Using different amounts of wild-type and mutant cells, little adhesion was observed in the presence of laminin and type I collagen. However, when fibronectin or vitronectin was used as substrate, there was an enhancement in the adhesion of wild-type and mutant cells. Only CHO-K1 cells showed a time-dependent adhesion on type IV collagen. These results suggest that the two cell lines present different adhesive profiles. Several lines of experimental evidence suggest that heparan sulfate proteoglycans play a role in cell adhesion as positive modulators of cell proliferation and as key participants in the process of cell division. Proliferation and cell cycle assays clearly demonstrate that a decrease in the amount of glycosaminoglycans does not inhibit the proliferation of mutant CHO-745 cells when compared to the wild type CHO-K1, in agreement with the findings that both CHO-K1 and CHO-745 cells take 8 h to enter the S phase.

Chemical treatment of papaya seeds aiming at long-term storage and control of damping off

Damping off is a nursery disease of great economic importance in papaya and seed treatment may be an effective measure to control. The aim of this work was to evaluate the quality of papaya seeds treated with fungicides and stored under two environmental and packaging conditions. Additionally, the efficiency of fungicide treatments in the control of damping-off caused by Rhizoctonia solani was evaluated. Papaya seeds were treated with the fungicides Captan, Tolylfluanid and the mixture Tolylfluanid + Captan (all commercial wettable powder formulations). Seeds of the control group were not treated. The seeds were stored for nine months in two conditions: packed in aluminum coated paper and kept at 7 ± 1ºC and in permeable kraft paper and kept in non-controlled environment. At the beginning of the storage and every three months the seed quality (germination and vigor tests), emergence rate index, height, dry mass and damping of plants in pre and post-emergence (in contaminated substrate and mycelia-free substrate) were analyzed. Both storage conditions as well as the fungicide treatments preserved the germination and seed vigor. In the infested substrate, seedling emergence was favored by fungicides, but in post-emergence, fungicides alone did not control the damping off caused by R. solani. Symptoms of damping off were not observed in the clean substrate. The results showed that the fungicide treatments may be used to pretreat papaya seed for long-term storage and commercialization.