Mortality In Tropical Regions Research Articles

Immunogenicity and Neutralization Potential of Recombinant Chimeric Protein Comprising the Catalytic Region of Gp63 of Leishmania and LTB against Leishmania donovani

Aim: To study the inhibition potential of antibody against a recombinant chimera comprising of the catalytic epitope of gp63 of Leishmania donovani and B subunit of heat-labile enterotoxin (LTB) in the functional activity of L. donovani. Background: Visceral leishmaniasis, caused by the protozoan parasite Leishmania donavani, is a major health problem and causes mortality in tropical regions. Protozoan proteases play a crucial role in the pathogenesis of the disease and in establishing infection by countering the host's innate immune responses, namely complement-mediated lysis and phagocytosis. A surface-bound metalloprotease (gp63) has been reported to be a major virulence factor resulting in the evasion of complement- mediated lysis, cleaving host extracellular and intracellular substrates, resulting in intra- phagolysosomal survival. Method: The epitope corresponding to the catalytic motif of gp63 of Leishmania donovani was fused with the B subunit of heat-labile enterotoxin, which is known to be immunogenic. The chimera was cloned to a prokaryotic expression vector and purified using Ni NTA affinity chromatography. Antibodies were generated against the purified fusion protein and analyzed for its ability to bind to the gp63 catalytic motif peptide by ELISA. The effect of fusion protein antibody on the functional activity of gp63 was evaluated by assessing the effect of purified IgGs on the protease activity and complement-mediated lysis of L. donovani promastigotes in vitro. Results: The present study reports that a recombinant chimera of the catalytic epitope of gp63 and B subunit of heat-labile enterotoxin (LTB) of E. coli, a potent adjuvant of humoral response can mount significant immune response towards the catalytic epitope. ELISA and Western blot analysis showed that the anti-fusion protein antiserum could recognize the native gp63. Also, it significantly inhibited the protease activity of promastigotes and subsequently increased complement-mediated lysis of the promastigotes in vitro. Conclusion: It could be concluded that the hybrid protein containing catalytic motif L. donovani gp63 protein and carrier protein (LTB) could elicit antibodies that could neutralise the functional activity of gp63 and thus could be a potential candidate for subunit leishmaniasis vaccine.

Drama as a community engagement strategy for malaria in rural Cambodia.

Background:Countries in Southeast Asia are working to eliminate multidrug-resistant falciparum malaria, a major cause of mortality in tropical regions. Malaria is declining but transmission persists in many rural areas and among forest workers and isolated populations. In these remote communities, conventional health services and education are limited. Mobilising and educating these populations require new approaches as many people are illiterate and do not attend village meetings. This article describes a qualitative study to assess the feasibility of a drama project as a community engagement strategy. Methods:A drama project was conducted in twenty villages in Cambodia with three key messages: to use insecticide-treated bednets and repellents, to get early diagnosis and treatment, and to learn about risks of forest-acquired malaria. Qualitative interviews were conducted with the drama team members, village malaria workers, local health staffs and villagers, to explore the feasibility of using drama to engage the community and the associated challenges. Results:29 people were interviewed, which included 18 semi-structured interviews and one focus group discussion. Analysis of the interviews resulted in development of the following seven themes: i) exposure to malaria and engagement activities, ii) readiness and barriers to participation, iii) understanding and learning about malaria using drama, iv) entertainment value and engagement method preferences, v) challenges to community engagement, vi) future participation and vii) sustainability. The event saw a very positive response, with an encouraging average participation rate of 66%. The project faced several challenges including logistic problems, rescheduling due to raining season, and time- and budget-constraints. Conclusions:Our evaluation demonstrated that the drama project was feasible in promoting awareness and understanding of malaria prevention and control. Audience members perceived drama as entertaining and as the preferred choice of engagement activity. Participatory drama could be considered as part of the community engagement for malaria elimination.

Functional characterization of a serine protease inhibitor modulated in the infection of the Aedes aegypti with dengue virus

During feeding with blood meal, female Aedes aegypti can transmit infectious agents, such as dengue, yellow fever, chikungunya and Zika viruses. Dengue virus causes human mortality in tropical regions of the world, and there is no specific treatment or vaccine with maximum efficiency being used for these infections. In the vector-virus interaction, the production of several molecules is modulated by both mosquitoes and invading agents. However, little information is available about these molecules in the Ae. aegypti mosquito during dengue infection. Inhibitors of the pacifastin family have been described to participate in the immune response of insects and Pac2 is the only gene of this family present in Ae. aegypti being then chosen for investigation. Pac2 was expressed in E. coli, purified and analyzed by mass spectrometry and SDS-PAGE. The Pac2 transcript was detected by qPCR, and its protein levels were assessed by Western blotting. The inhibitory activity of Pac2 was measured using its Ki, IC50 and zymography. Mosquito infections with DENV were introduced with the Brazilian ACS-46 DENV-2 strain propagated in C6/36 cells. In the present work, we showed that it is possibly involved in the interaction of the mosquitoes with the dengue virus. The Pac2 transcript was detected in larvae and in both the salivary gland and midgut of Ae. aegypti females, while the native protein was identified in females 3 h post-blood meal. Pac2 is a strong inhibitor of trypsin-like and thrombin-like proteases, which are present in 4th instar larvae midgut and females 24 h after blood meal. During DENV infection, up regulation of Pac2 expression occurs in the salivary gland and midgut. Pac2 is the first Pacifastin inhibitor member described in mosquitoes. Our results suggest that Pac2 acts on mosquito serine proteases, mainly the trypsin-like type, and is under transcriptional control by virus infection signals to allow its survival in the vector or by the mosquito as a defense mechanism against virus infection.

Drama as a community engagement strategy for malaria in rural Cambodia

Background: Countries in Southeast Asia are working to eliminate multidrug-resistant falciparum malaria, a major cause of mortality in tropical regions. Malaria is declining but transmission persists in many rural areas and among forest workers and isolated populations. In these remote communities, conventional health services and education are limited. Mobilising and educating these populations require new approaches as many people are illiterate and do not attend village meetings. This article describes a qualitative study to assess the feasibility of a drama project as a community engagement strategy. Methods: A drama project was conducted in twenty villages in Cambodia with three key messages: to use insecticide-treated bednets and repellents, to get early diagnosis and treatment, and to learn about risks of forest-acquired malaria. Qualitative interviews were conducted with the drama team members, village malaria workers, local health staffs and villagers, to explore the feasibility of using drama to engage the community and the associated challenges. Results: 29 people were interviewed, which included 18 semi-structured interviews and one focus group discussion. Analysis of the interviews resulted in development of the following seven themes: i) exposure to malaria and engagement activities, ii) readiness and barriers to participation, iii) understanding and learning about malaria using drama, iv) entertainment value and engagement method preferences, v) challenges to community engagement, vi) future participation and vii) sustainability. The event saw a very positive response, with an encouraging average participation rate of 66%. The project faced several challenges including logistic problems, rescheduling due to raining season, and time- and budget-constraints. Conclusions: Our evaluation demonstrated that the drama project was feasible in promoting awareness and understanding of malaria prevention and control. Audience members perceived drama as entertaining and as the preferred choice of engagement activity. Participatory drama could be considered as part of the community engagement for malaria elimination.

Drama as a community engagement strategy for malaria in rural Cambodia

Background: Countries in Southeast Asia are working to eliminate multidrug-resistant falciparum malaria, a major cause of mortality in tropical regions. Malaria is declining but transmission persists in many rural areas and among forest workers and isolated populations. In these remote communities, conventional health services and education are limited. Mobilising and educating these populations require new approaches as many people are illiterate and do not attend village meetings. This article describes a qualitative study to assess the feasibility of a drama project as a community engagement strategy. Methods: A drama project was conducted in twenty villages in Cambodia with three key messages: to use insecticide-treated bednets and repellents, to get early diagnosis and treatment, and to learn about risks of forest-acquired malaria. Qualitative interviews were conducted with the drama team members, village malaria workers, local health staffs and villagers, to explore the feasibility of using drama to engage the community and the associated challenges. Results: 29 people were interviewed, which included 18 semi-structured interviews and one focus group discussion. Analysis of the interviews resulted in development of the following seven themes: i) exposure to malaria and engagement activities, ii) readiness and barriers to participation, iii) understanding and learning about malaria using drama, iv) entertainment value and engagement method preferences, v) challenges to community engagement, vi) future participation and vii) sustainability. The event saw a very positive response, with an encouraging average participation rate of 66%. The project faced several challenges including logistic problems, rescheduling due to raining season, and time- and budget-constraints. Conclusions: Our evaluation demonstrated that the drama project was feasible in promoting awareness and understanding of malaria prevention and control. Audience members perceived drama as entertaining and as the preferred choice of engagement activity. Participatory drama could be considered as part of the community engagement for malaria elimination.

Attempt to control Haemonchus contortus in dairy goats with Barbervax®, a vaccine derived from the nematode gut membrane glycoproteins

The nematode Haemonchus contortus is the most important parasite of small ruminants around the world and the major cause of mortality in tropical regions. Goats are putatively more susceptible than sheep to this parasite and alternatives to anthelmintic utilization are constantly being sought especially after the rise of multiple anthelmintic resistance. Here we present results of a trial designed to evaluate Barbervax®, a vaccine containing gut proteins from Haemonchus contortus, in the control of haemoncosis in dairy goats. In this study female Saanen (n=20) and Anglo Nubian (n=20) goats aged six months were assigned by breed, body weight and fecal egg counts into four experimental groups (n=10) (vaccinated or non-vaccinated). Barbervax® was injected subcutaneously, starting with three priming doses 21days apart followed by boosts every 6 weeks. All animals grazed on the same bushland area and were subjected to natural and artificial worm infection. Mean efficacy over the trial period was 69.8±2.11% and 57.4±2.76% for the Anglo Nubians and Saanens, respectively. Significant differences in packed cell volume (PCV) and total plasma proteins (TPP) values were also observed but only in the Anglo Nubians. The protection afforded by vaccination was considered useful for management of Haemonchus infection in dairy goats by reducing egg counts. Furthermore, the vaccine does not generate chemical residues and could be very interesting for Haemonchus control during milk production.

Genetic resistance to natural coccidiosis infection in goats in a semi-arid region of India

AbstractCoccidiosis is one of the major causes of kid mortality in tropical regions and causes significant loss to farmers by affecting growth and feed efficiency in the growing kid. The strategy to control the coccidiosis is mainly through drug usage and is not efficacious at present. Therefore, an alternative strategy is required to control the disease in goats. Increasing genetic resistance to coccidiosis may be an appropriate complementary control strategy. The purpose of this study was to analyse the genetic variation in severity of natural coccidiosis infections in kids in the semi-arid region. The observations were recorded in 227 kids of Barbari and Jamunapari goats. Barbari goats had higher mean faecal oocyst counts (FOC) than Jamunapari goats at 3 and 6 months of age. The heritability for FOC was 0.05 and 0.15 at 3 and 6 months of age, respectively. All phenotypic and environmental correlations between FOC and live weight traits were low and negative, indicating a tendency for more heavily infec...

The Hidden Snake in the Grass: Superior Detection of Snakes in Challenging Attentional Conditions.

Snakes have provided a serious threat to primates throughout evolution. Furthermore, bites by venomous snakes still cause significant morbidity and mortality in tropical regions of the world. According to the Snake Detection Theory (SDT Isbell, 2006; 2009), the vital need to detect camouflaged snakes provided strong evolutionary pressure to develop astute perceptual capacity in animals that were potential targets for snake attacks. We performed a series of behavioral tests that assessed snake detection under conditions that may have been critical for survival. We used spiders as the control stimulus because they are also a common object of phobias and rated negatively by the general population, thus commonly lumped together with snakes as “evolutionary fear-relevant”. Across four experiments (N = 205) we demonstrate an advantage in snake detection, which was particularly obvious under visual conditions known to impede detection of a wide array of common stimuli, for example brief stimulus exposures, stimuli presentation in the visual periphery, and stimuli camouflaged in a cluttered environment. Our results demonstrate a striking independence of snake detection from ecological factors that impede the detection of other stimuli, which suggests that, consistent with the SDT, they reflect a specific biological adaptation. Nonetheless, the empirical tests we report are limited to only one aspect of this rich theory, which integrates findings across a wide array of scientific disciplines.

Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites

Background Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. Objective To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. Design From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992–2012, but two-thirds of the observations related to 2006–2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. Results Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. Conclusions The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.

Hypocalcemia is associated with disease severity in patients with dengue.

Dengue hemorrhagic fever (DHF) is a major cause of morbidity and mortality in tropical regions. Serum free calcium (Ca2+) is known to be important in cardiac and circulatory function. We evaluated association between serum Ca2+ level and severity of dengue. A cross-sectional study was carried out at a tertiary care private hospital in Sri Lanka. A probable case of dengue was diagnosed and classified according to World Health Organization criteria and confirmed by either IgM antibody, PCR, or NS1 antigen detection. Socio-demographic details were collected using an interviewer-administered questionnaire. The sample size was 135. The mean age was 26.1 years, and the majority were males (n = 80, 59.3%). DHF was diagnosed in 71 patients (52.6%). Mean serum Ca2+ level of the study population was 1.05 mmol/L (range 0.77-1.24). Mean serum Ca2+ was significantly higher in patients with dengue fever (DF) (1.09 mmol/L) than in those with DHF (1.02 mmol/L) (p < 0.05). A significant difference was observed between mean serum calcium levels of DHF I and DHF II. Prevalence of hypocalcemia in DHF and DF patients was 86.9% (n = 60) and 29.7% (n = 11), respectively (p < 0.05). Serum Ca2+ levels significantly correlated with dengue severity. Serum Ca2+ levels were significantly lower and hypocalcemia was more prevalent in patients with DHF than in patients with DF. Further studies are required to determine whether hypocalcemia can be utilized as a prognostic indicator and to evaluate effectiveness of calcium therapy in prevention of dengue complications.

The effects of season and meteorology on human mortality in tropical climates: a systematic review.

Research in the field of atmospheric science and epidemiology has long recognized the health effects of seasonal and meteorological conditions. However, little scientific knowledge exists to date about the impacts of atmospheric parameters on human mortality in tropical regions. Working within the scope of this systematic review, this investigation conducted a literature search using different databases; original research articles were chosen according to pre-defined inclusion and exclusion criteria. Both seasonal and meteorological effects were considered. The findings suggest that high amounts of rainfall and increasing temperatures cause a seasonal excess in infectious disease mortality and are therefore relevant in regions and populations in which such diseases are prevalent. On the contrary, moderately low and very high temperatures exercise an adverse effect on cardio-respiratory mortality and shape the mortality pattern in areas and sub-groups in which these diseases are dominant. Atmospheric effects were subject to population-specific factors such as age and socio-economic status and differed between urban and rural areas. The consequences of climate change as well as environmental, epidemiological and social change (e.g., emerging non-communicable diseases, ageing of the population, urbanization) suggest a growing relevance of heat-related excess mortality in tropical regions.

Humanized monoclonal antibody 2C9-cIgG has enhanced efficacy for yellow fever prophylaxis and therapy in an immunocompetent animal model

Yellow fever virus (YFV) causes significant human disease and mortality in tropical regions of South and Central America and Africa, despite the availability of an effective vaccine. No specific therapy for YF is available. We previously showed that the humanized monoclonal antibody (MAb) 2C9-cIgG provided prophylactic and therapeutic protection from mortality in interferon receptor-deficient strain AG129 mice challenged with YF 17D-204 vaccine. In this study we tested the prophylactic and therapeutic efficacy of this MAb against virulent YFV infection in an immunocompetent hamster model. Intraperitoneal (ip) administration of a single dose of MAb 2C9-cIgG 24h prior to YFV challenge resulted in significantly improved survival rates in animals treated with 380 or 38μg of MAb compared to untreated animals. Treatment with the higher dose also resulted in significantly improved weight gain and reductions in serum alanine aminotransferase (ALT) and virus titers in serum and liver. Prophylactic treatment with 2C9-cIgG 24h prior to virus challenge prevented the development of a virus-neutralizing antibody (vnAb) response in hamsters. Administration of a single ip dose of 380μg of 2C9-cIgG as late as 72h post-YFV challenge also resulted in significant improvement in survival rates. Hamsters treated at 4–72h post-virus challenge developed a robust vnAb response. Enhanced survival and improvement of various disease parameters in the hamster model when MAb 2C9-cIgG is administered up to 3days after virus challenge demonstrate the clinical potential of specific antibody therapy for YF.