Advantages and Limitations of Commercially Available Electrocuting Grids for Studying Mosquito Behaviour.

Mosquito feeding behaviour plays a major role in determining malaria transmission intensity and the impact of specific prevention measures. Human Landing Catch (HLC) is currently the only method that can directly and consistently measure the biting rates of anthropophagic mosquitoes, both indoors and outdoors. However, this method exposes the participant to mosquito-borne pathogens, therefore new exposure-free methods are needed to replace it. Commercially available electrocuting grids (EGs) were evaluated as an alternative to HLC using a Latin Square experimental design in Dar es Salaam, Tanzania. Both HLC and EGs were used to estimate the proportion of human exposure to mosquitoes occurring indoors (πi), as well as its two underlying parameters: the proportion of mosquitoes caught indoors (Pi) and the proportion of mosquitoes caught between the first and last hour when most people are indoors (Pfl). HLC and EGs methods accounted for 69% and 31% of the total number of female mosquitoes caught respectively and both methods caught more mosquitoes outdoors than indoors. Results from the gold standard HLC suggest that An. gambiae s.s. in Dar es Salaam is neither exophagic nor endophagic (Pi ≈ 0.5), whereas An. arabiensis is exophagic (Pi < < 0.5). Both species prefer to feed after 10 pm when most people are indoors (Pfl > >0.5). EGs yielded estimates of Pi for An. gambiae s.s., An. arabiensis and An. coustani, that were approximately equivalent to those with HLC but significantly underestimated Pfl for An. gambiae s.s. and An. coustani. The relative sampling sensitivity of EGs declined over the course of the night (p ≤ 0.001) for all mosquito taxa except An. arabiensis. Commercial EGs sample human-seeking mosquitoes with high sensitivity both indoors and outdoors and accurately measure the propensity of Anopheles malaria vectors to bite indoors rather than outdoors. However, further modifications are needed to stabilize sampling sensitivity over a full nocturnal cycle so that they can be used to survey patterns of human exposure to mosquitoes

Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

The RecX protein interacts with the RecA protein and modulates its activity in Herbaspirillum seropedicae

DNA repair is crucial to the survival of all organisms. The bacterial RecA protein is a central component in the SOS response and in recombinational and SOS DNA repairs. The RecX protein has been characterized as a negative modulator of RecA activity in many bacteria. The recA and recX genes of Herbaspirillum seropedicae constitute a single operon, and evidence suggests that RecX participates in SOS repair. In the present study, we show that the H. seropedicae RecX protein (RecXHs) can interact with the H. seropedicae RecA protein (RecAHs) and that RecAHs possesses ATP binding, ATP hydrolyzing and DNA strand exchange activities. RecXHs inhibited 90% of the RecAHs DNA strand exchange activity even when present in a 50-fold lower molar concentration than RecAHs. RecAHs ATP binding was not affected by the addition of RecX, but the ATPase activity was reduced. When RecXHs was present before the formation of RecA filaments (RecA-ssDNA), inhibition of ATPase activity was substantially reduced and excess ssDNA also partially suppressed this inhibition. The results suggest that the RecXHs protein negatively modulates the RecAHs activities by protein-protein interactions and also by DNA-protein interactions

Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8(+ )T cells by dendritic cells loaded with killed allogeneic breast cancer cells

INTRODUCTION: The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells ('cross-priming') is an important mechanism for induction of tumor specific immunity. METHODS: In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8(+ )T cells in 2-week and/or 3-week cultures. CD8(+ )T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-γ) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens. RESULTS: We found that DCs loaded with killed breast cancer cells can prime naïve CD8(+ )T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201(- )breast cancer cells can kill HLA-A*0201(+ )breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens, namely cyclin B1, MUC-1 and survivin. CONCLUSION: This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer

Adult population as potential reservoir of NTD infections in rural villages of Kwale district, Coastal Kenya: implications for preventive chemotherapy interventions policy

<p>Abstract</p> <p>Background</p> <p>Neglected tropical diseases (NTDs) are major public health problems in developing countries where they contribute to suffering of populations living in poor settings. As part of a research project started in September 2009 in Kwale district, Coast Region, Kenya, a baseline cross-sectional survey was conducted in 5 rural villages to provide information on the status of NTDs, including urinary schistosomiasis, soil-transmitted helminthiasis (STH), and lymphatic filariasis. This paper presents the results of a parasitological investigation among adults in the study villages.</p> <p>Methods</p> <p>A total of 599 adults in the 5 study villages were tested for NTD infections in urine, stool and blood. The presence of <it>Schistosoma haematobium </it>infection was determined by the urine filtration method. The presence of STH in stool was determined by Kato-Katz method while filarial antigenaemia was determined using immunochromatographic (ICT) test.</p> <p>Results</p> <p>The study revealed high prevalence of hookworm (41.7%) and schistosomiasis (18.2%) infections among adults in the study villages. Of the 599 individuals examined, 50.1% had one or more helminthic infections. There was low level of polyparasitism with helminthic NTDs in the study population with 9.5% and 1.7% of the participants having two and three infections, respectively.</p> <p>Conclusions</p> <p>In the current study, hookworm and schistosomiasis infections were identified as important infections among adults living in areas of high endemicity for these infections. Thus, if this section of the population is left untreated it may remain an important potential reservoir and a source of re-infection for school-age children treated in school deworming programmes. Therefore, there is a need to design novel strategies for preventive chemotherapy interventions that could allow inclusion of adults in an effort to reduce force of infection in high endemic communities.</p

Exploiting Anopheles responses to thermal, odour and visual stimuli to improve surveillance and control of malaria

Mosquito surveillance and control are at the heart of efforts to eliminate malaria, however, there remain significant gaps in our understanding of mosquito behaviour that impede innovation. We hypothesised that a combination of human-associated stimuli could be used to attract and kill malaria vectors more successfully than individual stimuli, and at least as well as a real human. To test this in the field, we quantified Anopheles responses to olfactory, visual and thermal stimuli in Burkina Faso using a simple adhesive trap. Traps baited with human odour plus high contrast visual stimuli caught more Anopheles than traps with odour alone, showing that despite their nocturnal habit, malaria vectors make use of visual cues in host-seeking. The best performing traps, however, combined odour and visual stimuli with a thermal signature in the range equivalent to human body temperature. When tested against a human landing catch during peak mosquito abundance, this “host decoy” trap caught nearly ten times the number of Anopheles mosquitoes caught by a human collector. Exploiting the behavioural responses of mosquitoes to the entire suite of host stimuli promises to revolutionise vector surveillance and provide new paradigms in disease control

Reproductive health issues in rural Western Kenya

<p>Abstract</p> <p>Background</p> <p>We describe reproductive health issues among pregnant women in a rural area of Kenya with a high coverage of insecticide treated nets (ITNs) and high prevalence of HIV (15%).</p> <p>Methods</p> <p>We conducted a community-based cross-sectional survey among rural pregnant women in western Kenya. A medical, obstetric and reproductive history was obtained. Blood was obtained for a malaria smear and haemoglobin level, and stool was examined for geohelminths. Height and weight were measured.</p> <p>Results</p> <p>Of 673 participants, 87% were multigravidae and 50% were in their third trimester; 41% had started antenatal clinic visits at the time of interview and 69% reported ITN-use. Malaria parasitemia and anaemia (haemoglobin < 11 g/dl) were detected among 36% and 53% of the women, respectively. Geohelminth infections were detected among 76% of the 390 women who gave a stool sample. Twenty percent of women were underweight, and sixteen percent reported symptoms of herpes zoster or oral thrush in the last two months. Nineteen percent of all women reported using a contraceptive method to delay or prevent pregnancy before the current pregnancy (injection 10%, pill 8%, condom 0.4%). Twenty-three percent of multigravidae conceived their current pregnancy within a year of the previous pregnancy. More than half of the multigravidae (55%) had ever lost a live born child and 21% had lost their last singleton live born child at the time of interview.</p> <p>Conclusion</p> <p>In this rural area with a high HIV prevalence, the reported use of condoms before pregnancy was extremely low. Pregnancy health was not optimal with a high prevalence of malaria, geohelminth infections, anaemia and underweight. Chances of losing a child after birth were high. Multiple interventions are needed to improve reproductive health in this area.</p

Feasibility and acceptability of home-based management of malaria strategy adapted to Sudan's conditions using artemisinin-based combination therapy and rapid diagnostic test

<p>Abstract</p> <p>Background</p> <p>Malaria remains a major public health problem especially in sub-Saharan Africa. Despite the efforts exerted to provide effective anti-malarial drugs, still some communities suffer from getting access to these services due to many barriers. This research aimed to assess the feasibility and acceptability of home-based management of malaria (HMM) strategy using artemisinin-based combination therapy (ACT) for treatment and rapid diagnostic test (RDT) for diagnosis.</p> <p>Methods</p> <p>This is a study conducted in 20 villages in Um Adara area, South Kordofan state, Sudan. Two-thirds (66%) of the study community were seeking treatment from heath facilities, which were more than 5 km far from their villages with marked inaccessibility during rainy season. Volunteers (one per village) were trained on using RDTs for diagnosis and artesunate plus sulphadoxine-pyrimethamine for treating malaria patients, as well as referral of severe and non-malaria cases. A system for supply and monitoring was established based on the rural health centre, which acted as a link between the volunteers and the health system. Advocacy for the policy was done through different tools. Volunteers worked on non-monetary incentives but only a consultation fee of One Sudanese Pound (equivalent to US$0.5).</p> <p>Pre- and post-intervention assessment was done using household survey, focus group discussion with the community leaders, structured interview with the volunteers, and records and reports analysis.</p> <p>Results and discussion</p> <p>The overall adherence of volunteers to the project protocol in treating and referring cases was accepted that was only one of the 20 volunteers did not comply with the study guidelines. Although the use of RDTs seemed to have improved the level of accuracy and trust in the diagnosis, 30% of volunteers did not rely on the negative RDT results when treating fever cases. Almost all (94.7%) the volunteers felt that they were satisfied with the spiritual outcome of their new tasks. As well, volunteers have initiated advocacy campaigns supported by their village health committees which were found to have a positive role to play in the project that proved their acceptability of the HMM design. The planned system for supply was found to be effective. The project was found to improve the accessibility to ACTs from 25% to 64.7% and the treatment seeking behaviour from 83.3% to 100% before- and after the HMM implementation respectivly.</p> <p>Conclusion</p> <p>The evaluation of the project identified the feasibility of the planned model in Sudan's condition. Moreover, the communities as well as the volunteers found to be satisfied with and supportive to the system and the outcome. The problem of treating other febrile cases when diagnosis is not malaria and other non-fever cases needs to be addressed as well.</p

Standardizing Operational Vector Sampling Techniques for Measuring Malaria Transmission Intensity: Evaluation of six Mosquito Collection Methods in Western Kenya.

Operational vector sampling methods lack standardization, making quantitative comparisons of malaria transmission across different settings difficult. Human landing catch (HLC) is considered the research gold standard for measuring human-mosquito contact, but is unsuitable for large-scale sampling. This study assessed mosquito catch rates of CDC light trap (CDC-LT), Ifakara tent trap (ITT), window exit trap (WET), pot resting trap (PRT), and box resting trap (BRT) relative to HLC in western Kenya to 1) identify appropriate methods for operational sampling in this region, and 2) contribute to a larger, overarching project comparing standardized evaluations of vector trapping methods across multiple countries. Mosquitoes were collected from June to July 2009 in four districts: Rarieda, Kisumu West, Nyando, and Rachuonyo. In each district, all trapping methods were rotated 10 times through three houses in a 3 × 3 Latin Square design. Anophelines were identified by morphology and females classified as fed or non-fed. Anopheles gambiae s.l. were further identified as Anopheles gambiae s.s. or Anopheles arabiensis by PCR. Relative catch rates were estimated by negative binomial regression. When data were pooled across all four districts, catch rates (relative to HLC indoor) for An. gambiae s.l (95.6% An. arabiensis, 4.4% An. gambiae s.s) were high for HLC outdoor (RR = 1.01), CDC-LT (RR = 1.18), and ITT (RR = 1.39); moderate for WET (RR = 0.52) and PRT outdoor (RR = 0.32); and low for all remaining types of resting traps (PRT indoor, BRT indoor, and BRT outdoor; RR < 0.08 for all). For Anopheles funestus, relative catch rates were high for ITT (RR = 1.21); moderate for HLC outdoor (RR = 0.47), CDC-LT (RR = 0.69), and WET (RR = 0.49); and low for all resting traps (RR < 0.02 for all). At finer geographic scales, however, efficacy of each trap type varied from district to district. ITT, CDC-LT, and WET appear to be effective methods for large-scale vector sampling in western Kenya. Ultimately, choice of collection method for operational surveillance should be driven by trap efficacy and scalability, rather than fine-scale precision with respect to HLC. When compared with recent, similar trap evaluations in Tanzania and Zambia, these data suggest that traps which actively lure host-seeking females will be most useful for surveillance in the face of declining vector densities

CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene

BACKGROUND: The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. METHODS: Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. RESULTS: Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. CONCLUSIONS: It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells