Background: Time series analysis is suitable for investigations of relatively direct and short-term effects of exposures on outcomes. In environmental epidemiology studies, this method has been one of the standard approaches to assess impacts of environmental factors on acute non-infectious diseases (e.g. cardiovascular deaths), with conventionally generalized linear or additive models (GLM and GAM). However, the same analysis practices are often observed with infectious diseases despite of the substantial differences from non-infectious diseases that may result in analytical challenges. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, systematic review was conducted to elucidate important issues in assessing the associations between environmental factors and infectious diseases using time series analysis with GLM and GAM. Published studies on the associations between weather factors and malaria, cholera, dengue, and influenza were targeted. Findings: Our review raised issues regarding the estimation of susceptible population and exposure lag times, the adequacy of seasonal adjustments, the presence of strong autocorrelations, and the lack of a smaller observation time unit of outcomes (i.e. daily data). These concerns may be attributable to features specific to infectious diseases, such as transmission among individuals and complicated causal mechanisms. Conclusion: The consequence of not taking adequate measures to address these issues is distortion of the appropriate risk quantifications of exposures factors. Future studies should pay careful attention to details and examine alternative models or methods that improve studies using time series regression analysis for environmental determinants of infectious diseases.

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Background: In the Democratic Republic of Congo (DRC), few studies have focused on treatment-seeking paths selected by caretakers for the management of severe childhood malaria in an urban environment. The present study aims at describing the treatment-seeking paths according to the characteristics of households, as well as the subsequent impact on pre-hospitalisation delay and malarial fatality and on the main syndromes associated with severe childhood malaria. Methods: This descriptive study included data collected at nine hospitals in Kinshasa between January and November 2011. A total of 1,350 children, under 15 years of age and hospitalised for severe malaria, were included in the study. Results: Regarding the management of malaria, 31.5% of households went directly to the health centre or hospital while 68.5% opted for self-medication, church and/or traditional healing therapy. The most frequent first-line option was self-medication, adopted by more than 61.5% of households. Nevertheless, rational self-medication using antimalarial drugs recommended by the WHO (artemisinin-based combinations) was reported for only 5.5% of children. Only 12.5% of households combined 2 or 3 traditional options. The following criteria influenced the choice of a modern vs. traditional path: household socioeconomic level, residential environment, maternal education level and religious beliefs. When caretakers opted for traditional healing therapy, the pre-hospitalisation delay was longer and the occurrence of respiratory distress, severe anaemia and mortality was higher. Conclusion: The implementation of a malaria action plan in the Democratic Republic of Congo should take into account the diversity and pluralistic character of treatment-seeking behaviours in order to promote the most appropriate options (hospital and rational self-medication) and to avoid detrimental outcomes.

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To understand the molecular epidemiology of circulating dengue viruses (DENV) in Upper Myanmar, DENV isolation was attempted by inoculating the sera of a panel of 110 serum samples onto a C6/36 mosquito cell line. The samples were collected from dengue (DEN) patients admitted at Mandalay Children’s Hospital in 2006. Infected culture fluids were subjected to a RT-PCR to detect the DENV genome. Three DENV strains were isolated. This was the first DENV isolation performed either in Mandalay or in Upper Myanmar. One strain belonged to DENV serotype-3 (DENV-3), and two other strains belonged to DENV serotype-4 (DEN-4). The sequence data for the envelope gene of these strains were used in a phylogenetic comparison of DENV-3 and DENV-4 from various countries. Phylogenetic analyses revealed that this DENV-3 strain was clustered within genotype II, and the two DENV-4 strains were clustered within genotype I in each serotype. The Myanmar strains were closely related to strains from the neighboring countries of Thailand and Bangladesh. These results are important for elucidating the trends of recent and future DEN outbreaks in Myanmar.

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Background: The health impacts of climate change are an issue of growing concern in the Pacific region. Prior to 2010, no formal, structured, evidence-based approach had been used to identify the most significant health risks posed by climate change in Pacific island countries. During 2010 and 2011, the World Health Organization supported the Federated States of Micronesia (FSM) in performing a climate change and health vulnerability and adaptation assessment. This paper summarizes the priority climate-sensitive health risks in FSM, with a focus on diarrheal disease, its link with climatic variables and the implications of climate change. Methods: The vulnerability and adaptation assessment process included a review of the literature, extensive stakeholder consultations, ranking of climate-sensitive health risks, and analysis of the available long-term data on climate and climate-sensitive infectious diseases in FSM, which involved examination of health information data from the four state hospitals in FSM between 2000 and 2010; along with each state’s rainfall, temperature and El Niño-Southern Oscillation data. Generalized linear Poisson regression models were used to demonstrate associations between monthly climate variables and cases of climate-sensitive diseases at differing temporal lags. Results: Infectious diseases were among the highest priority climate-sensitive health risks identified in FSM, particularly diarrheal diseases, vector-borne diseases and leptospirosis. Correlation with climate data demonstrated significant associations between monthly maximum temperature and monthly outpatient cases of diarrheal disease in Pohnpei and Kosrae at a lag of one month and 0 to 3 months, respectively; no such associations were observed in Chuuk or Yap. Significant correlations between disease incidence and El Niño-Southern Oscillation cycles were demonstrated in Kosrae state. Conclusions: Analysis of the available data demonstrated significant associations between climate variables and climate-sensitive infectious diseases. This information should prove useful in implementing health system and community adaptation strategies to avoid the most serious impacts of climate change on health in FSM.

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Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.

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We produced a transgenic rodent malaria parasite (Plasmodium berghei) that contained the luciferase gene under a promoter region of elongation factor-1α. These transgenic (TG) parasites expressed luciferase in all stages of their life cycle, as previously reported. However, we were the first to succeed in observing sporozoites as a mass in mouse skin following their deposition by the probing of infective mosquitoes. Our transgenic parasites may have emitted stronger bioluminescence than previous TG parasites. The estimated number of injected sporozoites by mosquitoes was between 34 and 775 (median 80). Since luciferase activity diminished immediately after the death of the parasites, luciferase activity could be an indicator of the existence of live parasites. Our results indicated that sporozoites survived at the probed site for more than 42 hours. We also detected sporozoites in the liver within 15 min of the intravenous injection. Bioluminescence was not observed in the lung, kidney or spleen. We confirmed the observation that the liver was the first organ in which malaria parasites entered and increased in number.

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As part of efforts to develop an informed policy for rotavirus vaccination, this prospective study was conducted to estimate the burden of rotavirus diarrhea among children less than 5 years old attended to the Department of Pediatrics, Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Thimphu, Bhutan. The duration of the study was three years, extending from February 2010 through December 2012. We estimated the frequency of hospitalization in the pediatric ward and dehydration treatment unit (DTU) for diarrhea and the number of events attributable to rotavirus infection among children under 5 years of age. During the study period, a total of 284 children (1 in 45) were hospitalized in the pediatric ward, and 2,220 (1 in 6) in the DTU with diarrhea among children residing in the Thimphu district. Group A rotavirus was detected in 32.5% and 18.8% of the stool samples from children hospitalized in the pediatric ward, respectively. Overall, 22.3% of the stool samples were rotavirus-positive, and the majority (90.8%) of them was detected in children under 2 years of age. From this study, we estimated that the annual incidence of hospitalization in the pediatric ward and DTU due to rotavirus diarrhea was 2.4/1000 (95% CI 1.7–3.4) and 10.8/1000 (95% CI 9.1–12.7) children, respectively. This study revealed that rotavirus is a major cause of diarrhea in Bhutanese children in Thimphu district and since no study has been performed previously, represents an important finding for policy discussions regarding the adoption of a rotavirus vaccine in Bhutan.

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Background. In developed countries, typhoid fever is a travel-associated disease that is often overlooked. However, as standard blood and stool culture methods have relatively low sensitivity, diagnosis depends heavily on clinical signs and symptoms and on a high level of suspicion. Methods. Reported here is the case of an 18-year-old male who presented with fever and acute scrotal ulcers and whose blood cultures were positive for Salmonella enterica serotype Typhi. A review of genital ulcers associated with typhoid fever in the literature is discussed. Conclusion. This report suggests that typhoid fever is a differential diagnosis of acute genital ulcers.

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The eco-epidemiology of American cutaneous leishmaniasis (ACL) is driven by animal reservoir species that are a source of infection for sand flies that serve as vectors infecting humans with Leishmania spp parasites. The emergence and re-emergence of this disease across Latin America calls for further studies to identify reservoir species associated with enzootic transmission. Here, we present results from a survey of 52 individuals from 13 wild mammal species at endemic sites in Costa Rica and Panama where ACL mammal hosts have not been previously studied. For Leishmania spp. diagnostics we employed a novel PCR technique using blood samples collected on filter paper. We only found Leishmania spp parasites in one host, the two-toed sloth, Choloepus hoffmanni. Our findings add further support to the role of two-toed sloths as an important ACL reservoir in Central America.

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