Tropical Medicine and Infectious Disease — Open Access Journal

Cell-based screening has become the major compound interrogation strategy in Chagas disease drug discovery. Several different cell lines have been deployed as host cells in screening assays. However, host cell characteristics and host-parasite interactions may play an important role when assessing anti-T. cruzi compound activity, ultimately impacting on hit discovery. To verify this hypothesis, four distinct mammalian cell lines (U2OS, THP-1, Vero and L6) were used as T. cruzi host cells in High Content Screening assays. Rates of infection varied greatly between different host cells. Susceptibility to benznidazole also varied, depending on the host cell and parasite strain. A library of 1,280 compounds was screened against the four different cell lines infected with T. cruzi, resulting in the selection of a total of 82 distinct compounds as hits. From these, only two hits were common to all four cell lines assays (2.4%) and 51 were exclusively selected from a single assay (62.2%). Infected U2OS cells were the most sensitive assay, as 55 compounds in total were identified as hits; infected THP-1 yielded the lowest hit rates, with only 16 hit compounds. Of the selected hits, compound FPL64176 presented selective anti-T. cruzi activity and could serve as a starting point for the discovery of new anti-chagasic drugs. Full article

Background: This is a retrospective, analytic observational study where we describe cases of sporotrichosis and mycetoma from Acapulco General Hospital and Community Dermatology Mexico C.A. over 25 years. Analysis of environmental features that favour the development of such diseases has been made, as well as the limitations in the study and treatment of such diseases in resource poor settings. Methods: We reviewed the information on 76 sporotrichosis and 113 mycetoma patients out of a total of 14,000 consultations at Acapulco General Hospital and from Community Dermatology clinics. We analysed the epidemiological and mycological characteristics and the investigations used for diagnosis such as direct examination, culture, intradermal test reactions, and biopsy. Results: In total 91 confirmed cases of actinomycetoma, 22 of eumycetoma and 76 of sporotrichosis have been identified including diagnostic studies for both diseases and their treatment. Discussion: The results obtained have been analysed and interpreted in patients with mycetoma and sporotrichosis in the state of Guerrero, México, along with limitations in their management in areas with limited economic and logistical resources. The prevalence of mycetoma in our setting is compared with other centres where patients from all over the country are seen. The possible causes for variations in prevalence in specific areas has been looked for, in one of the poorest states of the Mexican Republic. Full article

Armillifer is a genus of obligate parasites belonging to the Pentastomida subclass that was first described as a cause of human disease in 1847. Human infection by Armillifer is rare and not widely known. These parasites are transmitted to humans by handling or eating undercooked meat from infected snakes, which are the definitive hosts, or oral uptake of environmental ova. The aim of this systematic review was to record all available evidence regarding infections by Armillifer in humans. A systematic review of PubMed (through 21 December 2018) for studies providing epidemiological, clinical, microbiological, as well as treatment data and outcomes of Armillifer infections was conducted. A total of 26 studies, containing data of 40 patients, were eventually included in the analysis. The most common sites of infection were the peritoneal cavity, the liver, the lower respiratory and the abdominal tract. The commonest infecting species was A. armillatus and most patients were asymptomatic; however, when symptoms occurred, the commonest was abdominal pain, even though unusual presentations occurred, such as hepatic encephalopathy or neurologic symptoms. Most cases were diagnosed at surgery or by imaging, and most patients were not treated. Mortality was low, but the majority of the cases with ocular infection lead to permanent loss of vision. Full article

A nationwide prevention and control campaign for leptospirosis in Thailand has led to a decreased incidence rate, but the mortality and case fatality rates have remained stable. Regarding the limited knowledge of risk factors, a case-control study of the association between environmental and behavioral exposure with severe leptospirosis was implemented to identify the risk factors among adults in Thailand. The study was conducted in 12 hospital-based sites. Hospitalized patients with suspected clinical symptoms of leptospirosis were tested for leptospirosis by culture, loop mediated isothermal amplification (LAMP), real-time PCR, and the microscopic agglutination test (MAT). All participants answered a standardized questionnaire about potential risk factors. Risk factors were identified by univariable and multivariable logistic regression. Of the 44 confirmed cases, 33 (75.0%) presented with severe illness, as determined by clinical criteria, and were categorized as severe cases. Non-severe cases were defined as patients with non-severe symptoms of leptospirosis. Living nearby a rubber tree plantation (adjusted OR 11.65, 95% CI 1.08–125.53) and bathing in natural bodies of water (adjusted OR 10.45, 95% CI 1.17–93.35) were both significantly associated with an increased risk of severe leptospirosis. We recommend designating rubber plantations in Thailand as high-risk zones and closely monitoring hospitalized patients in those areas. Full article

With the rapid development and broad applications of next-generation sequencing platforms and bioinformatic analytical tools, genomics has become a popular area for biosurveillance and international scientific collaboration. Governments from countries including the United States (US), Canada, Germany, and the United Kingdom have leveraged these advancements to support international cooperative programs that aim to reduce biological threats and build scientific capacity worldwide. A recent conference panel addressed the impacts of the enhancement of genomic sequencing capabilities through three major US bioengagement programs on international scientific engagement and biosecurity risk reduction. The panel contrasted the risks and benefits of supporting the enhancement of genomic sequencing capabilities through international scientific engagement to achieve biological threat reduction and global health security. The lower costs and new bioinformatic tools available have led to the greater application of sequencing to biosurveillance. Strengthening sequencing capabilities globally for the diagnosis and detection of infectious diseases through mutual collaborations has a high return on investment for increasing global health security. International collaborations based on genomics and shared sequence data can build and leverage scientific networks and improve the timeliness and accuracy of disease surveillance reporting needed to identify and mitigate infectious disease outbreaks and comply with international norms. Further efforts to promote scientific transparency within international collaboration will improve trust, reduce threats, and promote global health security. Full article

Bats can host pathogenic organisms such as viruses and fungi, but little is known about the pathogenicity of their parasites. Hemoparasites are frequently recorded in Neotropical bats, particularly Litomosoides (Filarioidea: Onchocercidae), but their pathogenic effect on bats is scarcely known. In this work, Litomosoides microfilariae were identified in four (8%) out of 51 sampled frugivorous bats belonging to three different species: Artibeus aztecus, Artibeus jamaicensis, and Artibeus lituratus, which are located in Yautepec, Morelos, Mexico. Two infected animals showed weakness, tachypnoea, and ecchymosis on their wings. In these animals, histopathology revealed microfilariae in the blood vessels of the lung, liver, and spleen. Both animals presented exudative pneumonia with congestion and concomitant edema, in addition to moderate arterial hypertrophy. Parasitemia was quantified in blood samples of the infected animals (>3000 parasites/mL). Phylogenetic analysis placed the obtained sequence inside the Litomosoides genus, reaching over 98% identity to the related species. Due to the relevance of bats in ecosystems, any new record of their parasite repertoire offers noteworthy insights into our understanding of the ecology and impact of new parasite species in bats. Full article

In spite of spectacular progress towards the goal of elimination of schistosomiasis, particularly in China but also in other areas, research gaps and outstanding issues remain. Although expectations of achieving elimination of this disease have never been greater, all constraints have not been swept aside. Indeed, there are some formidable obstacles, such as insufficient amounts of drugs to treat everybody and still limited use of high-sensitive diagnostic techniques, both for the definitive and the intermediate hosts, which indicate that prevalence is considerably underrated in well-controlled areas. Elimination will be difficult to achieve without a broad approach, including a stronger focus on transmission, better diagnostics and the establishment of a reliable survey system activating a rapid response when called for. Importantly, awareness of the crucial importance of transmission has been revived resulting in renewed interest in snail control together with more emphasis on health education and sanitation. The papers collected in this special issue entitled ‘Prospects for Schistosomiasis Elimination’ reflect these issues and we are particularly pleased to note that some also discuss the crucial question when to declare a country free of schistosomiasis and present techniques that together create an approach that can show unequivocally when interruption of transmission has been achieved. Full article

Scrub typhus, a chigger-borne febrile illness, occurs primarily in countries of the Asia-Pacific rim and islands of the Western Pacific. The etiologic agent is the obligate intracellular rickettsial bacterium Orientia tsutsugamushi. Research on O. tsutsugamushi has relied on the availability of several prototype strains, which were isolated from human cases of scrub typhus in the 1940s and 1950s. We review the history of the three original, and most important, prototype strains, Gilliam, Karp and Kato, including information on their isolation, their culture history, their clinical characteristics, their importance within the research literature on scrub typhus, and recent advances in elucidating their molecular genomics. The importance of these strains to the research and development of clinical tools related to scrub typhus is also considered. Finally, we examine whether the strains have been genetically stable since their isolation, and whether prototype strains maintained in separate laboratories are identical, based on pairwise comparisons of several sequences from four genes. By using genetic information archived in international DNA databases, we show that the prototype strains used by different laboratories are essentially identical, and that the strains have retained their genetic integrity at least since the 1950s. The three original prototype strains should remain a standard by which new diagnostic procedures are measured. Given their fundamental position in any comparative studies, they are likely to endure as a critical part of present and future research on scrub typhus and Orientia. Full article

Tuberculosis (TB) mortality declined after the 1918 pandemic, suggesting that influenza killed those who would have died from TB. Few studies have analyzed TB as a direct risk factor for 1918 influenza morbidity and mortality by age and sex. We study the impacts of TB on influenza-like illness (% of population sick) and case fatality (% of cases dying) by age and sex through case-control comparisons of patients (N = 201) and employees (N = 97) from two Norwegian sanatoriums. Female patients, patients at Landeskogen sanatorium, and patients aged 10–39 years had significantly lower morbidity than the controls. None of the 62 sick employees died, while 15 of 84 sick patients did. The case-control difference in case fatality by sex was only significant for females at Lyster sanatorium and females at both sanatoriums combined. Non-significant case-control differences in case fatality for males were likely due to small samples. Patients 20–29 years for both sexes combined at Lyster sanatorium and at both sanatoriums combined, as well as females 20–29 years for both sanatoriums combined, had significantly higher case fatality. We conclude that TB was associated with higher case fatality, but morbidity was lower for patients than for employees. The results add to the study of interactions between bacterial and viral diseases and are relevant in preparing for pandemics in TB endemic areas. Full article

Introduction: Soil-transmitted helminths (STHs) are gastrointestinal parasites widely distributed in tropical and subtropical areas. Mass drug administration (MDA) of benzimidazoles (BZ) is the most recommended for STH control. These drugs have demonstrated limited efficacy against Trichuris trichiura and the long-term use of single-dose BZ has raised concerns of the possible emergence of genetic resistance. The objective of this investigation was to determine whether genetic mutations associated with BZ resistance were present in STH species circulating in an endemic region of Honduras. Methods: A parasitological survey was performed as part of this study, the Kato–Katz technique was used to determine STH prevalence in children of La Hicaca, Honduras. A subgroup of children received anthelminthic treatment in order to recover adult parasite specimens that were analyzed through molecular biology techniques. Genetic regions containing codons 200, 198, and 167 of the β-tubulin gene of Ascaris lumbricoides and Trichuris trichiura were amplified and sequenced. Results: Stool samples were collected from 106 children. The overall STH prevalence was 75.47%, whereby T. trichiura was the most prevalent helminth (56.6%), followed by A. lumbricoides (17%), and hookworms (1.9%). Eighty-five sequences were generated for adjacent regions to codons 167, 198, and 200 of the β-tubulin gene of T. trichiura and A. lumbricoides specimens. The three codons of interest were found to be monomorphic in all the specimens. Conclusion: Although the inability to find single-nucleotide polymorphisms (SNPs) in the small sample analyzed for the present report does not exclude the possibility of their occurrence, these results suggest that, at present, Honduras’s challenges in STH control may not be related to drug resistance but to environmental conditions and/or host factors permitting reinfections. Full article

Influenza A viruses (IAVs) infect humans and a wide range of animal species in nature, and waterfowl and shorebirds are their reservoir hosts. Of the 18 haemagglutinin (HA) and 11 neuraminidase (NA) subtypes of IAV, 16 HA and 9 NA subtypes infect aquatic birds. However, among the diverse pool of IAVs in nature, only a limited number of animal IAVs cross the species barrier to infect humans and a small subset of those have spread efficiently from person to person to cause an influenza pandemic. The ability to infect a different species, replicate in the new host and transmit are three distinct steps in this process. Viral and host factors that are critical determinants of the ability of an avian IAV to infect and spread in humans are discussed. Full article

The tuberculosis (TB) health burden in Fiji has been declining in recent years, although challenges remain in improving control of the diabetes co-epidemic and achieving adequate case detection across the widely dispersed archipelago. We applied a mathematical model of TB transmission to the TB epidemic in Fiji that captured the historical reality over several decades, including age stratification, diabetes, varying disease manifestations, and incorrect diagnoses. Next, we simulated six intervention scenarios that are under consideration by the Fiji National Tuberculosis Program. Our findings show that the interventions were able to achieve only modest improvements in disease burden, with awareness raising being the most effective intervention to reduce TB incidence, and treatment support yielding the highest impact on mortality. These improvements would fall far short of the ambitious targets that have been set by the country, and could easily be derailed by moderate increases in the diabetes burden. Furthermore, the effectiveness of the interventions was limited by the extensive pool of latent TB infection, because the programs were directed at only active cases, and thus were unlikely to achieve the desired reductions in burden. Therefore, it is essential to address the co-epidemic of diabetes and treat people with latent TB infection. Full article

Brucellosis is endemic among dairy animals in India, contributing to production losses and posing a health risk to people, especially farmers and others in close contact with dairy animals or their products. Growing urban populations demand increased milk supplies, resulting in intensifying dairy production at the peri-urban fringe. Peri-urban dairying is under-studied but has implications for disease transmission, both positive and negative. In this cross-sectional study, five Indian cities were selected to represent different geographies and urbanization extent. Around each, we randomly selected 34 peri-urban villages, and in each village three smallholder dairy farms (defined as having a maximum of 10 dairy animals) were randomly selected. The farmers were interviewed, and milk samples were taken from up to three animals. These were tested using a commercial ELISA for antibodies against Brucella abortus, and factors associated with herd seroprevalence were identified. In all, 164 out of 1163 cows (14.1%, 95% CI 12.2–16.2%) were seropositive for Brucella. In total, 91 out of 510 farms (17.8%, 95% CI 14.6–21.4%) had at least one positive animal, and out of these, just seven farmers stated that they had vaccinated against brucellosis. In four cities, the farm-level seroprevalence ranged between 1.4–5.2%, while the fifth city had a seroprevalence of 72.5%. This city had larger, zero-grazing herds, used artificial insemination to a much higher degree, replaced their animals by purchasing from their neighbors, were less likely to contact a veterinarian in case of sick animals, and were also judged to be less clean. Within the high-prevalence city, farms were at higher risk of being infected if they had a young owner and if they were judged less clean. In the low-prevalence cities, no risk factors could be identified. In conclusion, this study has identified that a city can have a high burden of infected animals in the peri-urban areas, but that seroprevalence is strongly influenced by the husbandry system. Increased intensification can be associated with increased risk, and thus the practices associated with this, such as artificial insemination, are also associated with increased risk. These results may be important to identify high-risk areas for prioritizing interventions and for policy decisions influencing the structure and development of the dairy industry. Full article

Bartonella spp. bacteria can be found around the globe and are the causative agents of multiple human diseases. The most well-known infection is called cat-scratch disease, which causes mild lymphadenopathy and fever. As our knowledge of these bacteria grows, new presentations of the disease have been recognized, with serious manifestations. Not only has more severe disease been associated with these bacteria but also Bartonella species have been discovered in a wide range of mammals, and the pathogens’ DNA can be found in multiple vectors. This review will focus on some common mammalian reservoirs as well as the suspected vectors in relation to the disease transmission and prevalence. Understanding the complex interactions between these bacteria, their vectors, and their reservoirs, as well as the breadth of infection by Bartonella around the world will help to assess the impact of Bartonellosis on public health. Full article

Zika virus is an emerging mosquito-borne flavivirus that recently caused a large epidemic in Latin America characterized by novel disease phenotypes, including Guillain-Barré syndrome, sexual transmission, and congenital anomalies, such as microcephaly. This epidemic, which was declared an international public health emergency by the World Health Organization, has highlighted shortcomings in our current understanding of, and preparation for, emerging infectious diseases in general, as well as challenges that are specific to Zika virus infection. Vaccine development for Zika virus has been a high priority of the public health response, and several candidates have shown promise in pre-clinical and early phase clinical trials. The optimal selection and implementation of imperfect serologic assays are among the crucial issues that must be addressed in order to advance Zika vaccine development. Here, I review key considerations for how best to incorporate into Zika vaccine trials the existing serologic tools, as well as those on the horizon. Beyond that, this discussion is relevant to other intervention strategies to combat Zika and likely other emerging infectious diseases. Full article

Influenza antivirals will play a critical role in the treatment of outpatients and hospitalised patients in the next pandemic. In the past decade, a number of new influenza antivirals have been licensed for seasonal influenza, which can now be considered for inclusion into antiviral stockpiles held by the World Health Organization (WHO) and individual countries. However, data gaps remain regarding the effectiveness of new and existing antivirals in severely ill patients, and regarding which monotherapy or combinations of antivirals may yield the greatest improvement in outcomes. Regardless of the drug being used, influenza antivirals are most effective when treatment is initiated early in the course of infection, and therefore in a pandemic, effective strategies which enable rapid diagnosis and prompt delivery will yield the greatest benefits. Full article

In 1996, schistosomiasis due to Schistosoma japonicum was declared eradicated in Japan. In the People’s Republic of China, S. japonicum transmission has been interrupted in the major endemic areas in the coastal plains but the disease persists in the lake and marshland regions south of the Yangtze River. The disease remains a public health problem in endemic areas in the Philippines and in isolated areas in Indonesia. Comprehensive multidisciplinary campaigns had led to eradication of schistosomiasis in Japan and have been successful in the interruption of disease transmission in the major endemic regions of the People’s Republic of China. Unfortunately, the integrated measures cannot be duplicated in schistosomiasis endemic areas in the Philippines because of limited resources. The problem is also more complicated due to the topography in the Philippines and transmission is not seasonal as in China. An innovative approach is needed in the Philippines if schistosomiasis elimination is the goal. Full article

For many years, researchers have postulated that helminthic infections may increase susceptibility to HIV, and that immune activation may have contributed to the extensive spread of HIV in sub-Saharan Africa. In the meantime, immunological studies have provided some evidence in support of this hypothesis, while cross-sectional clinical studies were able to further support the assumed association between HIV infection and selected helminthic co-infections. However, as many of the helminthic infections relevant to HIV-infected patients belong to the group of “neglected tropical diseases”, as defined by the World Health Organization, a certain lack of attention has inhibited progress in fully scaling up treatment and prevention efforts. In addition, despite the fact that the challenges of co-infections have preoccupied clinicians for over two decades, relevant research questions remain unanswered. The following review aims to provide a concise overview of associations between HIV and selected helminthic co-infections concerning aspects of HIV acquisition and transmission, clinical and immunological findings in co-infected individuals, as well as treatment and prevention efforts. Full article

In Africa, pathogens transmitted by ticks are of major concern in livestock production and human health. Despite noticeable improvements particularly of molecular screening methods, their widespread availability and the detection of multiple infections remain challenging. Hence, we developed a universally accessible and robust tool for the detection of bacterial pathogens and piroplasmid parasites of cattle. A low-cost and low-density chip DNA microarray kit (LCD-Array) was designed and tested towards its specificity and sensitivity for five genera causing tick-borne diseases. The blood samples used for this study were collected from cattle in Northern Cameroon. Altogether, 12 species of the genera Anaplasma, Ehrlichia, Rickettsia and Theileria, and their corresponding genus-wide probes including Babesia were tested on a single LCD-Array. The detection limit of plasmid controls by PCR ranged from 1 to 75 copies per µL depending on the species. All sequenced species hybridized on the LCD-Array. As expected, PCR, agarose gel electrophoresis and Sanger sequencing found significantly less pathogens than the LCD-Array (p < 0.001). Theileria and Rickettsia had lower detection limits than Anaplasma and Ehrlichia. The parallel identification of some of the most detrimental tick-borne pathogens of livestock, and the possible implementation in small molecular-diagnostic laboratories with limited capacities makes the LCD-Array an appealing asset. Full article