Tropical Medicine and Infectious Disease — Open Access Journal

The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbiont. This new-found interest prompted the eventual organization of the Anti-Wolbachia Consortium (A-WOL) at the Liverpool School of Tropical Medicine, who, among others have been active in the field of antiwolbachial drug discovery to treat filarial infections. Clinical proof of concept studies using doxycycline demonstrated the utility of the antiwolbachial therapy, but efficacious treatments were of long duration and not safe for all infected. With the advance of robotics, automation, and high-speed computing, the search for superior antiwolbachials shifted away from smaller studies with a select number of antibiotics to high-throughput screening approaches, centered largely around cell-based phenotypic screens due to the rather limited knowledge about, and tools available to manipulate, this bacterium. A concomitant effort was put towards developing validation approaches and in vivo models supporting drug discovery efforts. In this review, we summarize the strategies behind and outcomes of recent large phenotypic screens published within the last 5 years, hit compound validation approaches and promising candidates with profiles superior to doxycycline, including ones positioned to advance into clinical trials for treatment of filarial worm infections. Full article

Indonesia has the third highest tuberculosis (TB) caseload internationally. A cornerstone for strengthening health systems to respond to TB is a well-trained workforce. In a partnership between Indonesian and Australian institutions, TB training was run during 2018 to strengthen the local capacity to meet End TB strategy targets. This paper aims to report on course design, delivery, training outcomes, and reflections. Seventy-six Indonesian healthcare workers, program staff, researchers, and policy-makers were selected from over 800 applicants. The structure comprised three trainings, each with a pre-course workshop (in Indonesia) to identify learning needs, a two-week block (Australia), and a post-course workshop (Indonesia). The training content delivered was a combination of TB technical knowledge and program/project theory, design, and logic, and the training utilised multiple teaching and learning methods. An innovative element of the training was participant-designed TB workplace projects focusing on context-specific priorities. Evaluation was undertaken using participant surveys and appraisal of the projects. Participants rated the course highly, while success in project implementation varied. Reflections include the importance of involving Indonesian experts in delivery of training, the need to understand participant learning requirements and adapt the training content accordingly, and the challenge of measuring tangible training outputs. Full article

Ternidens deminutus, the false hookworm of humans and non-human primates, represents a truly neglected intestinal helminth infection. The similarity of the eggs of this nematode to those of hookworm both presents a diagnostic challenge and a potential confounder in prevalence surveys of soil transmitted helminths (STH) in regions where T. deminutus is found. The helminth infects non-human primates throughout Africa and Asia, but reports of human infection are almost exclusively found in eastern and southern Africa. Historically, an infection prevalence up to 87% has been reported from some parts of Zimbabwe. Scarce reports of ternidensiasis have also been made in individuals in Suriname and one from Thailand. Little work has been performed on this parasite since the 1970s and it not known why human infection has not been reported more widely or what the current prevalence in humans from historically endemic areas is. This review serves to revisit this enigmatic parasite and provide detail to a modern audience of parasitologists on its history, clinical presentation, geographic distribution, life cycle, biology, morphology, diagnosis and treatment. Full article

Recent studies in Cameroon after 20 years of implementation of the Community Directed Treatment with ivermectin (CDTI) strategy, revealed mixed results as regards community ownership. This brings into question the feasibility of Community Directed Interventions (CDI) in the country. We carried out qualitative surveys in 3 health districts of Cameroon, consisting of 11 individual interviews and 10 Focus Group Discussions (FGDs) with specific community members. The main topic discussed during individual interviews and FGDs was about community participation in health. We found an implementation gap in CDTI between the process theory in the 3 health districts. Despite this gap, community eagerness for health information and massive personal and financial adhesion to interventions that were perceived important, were indicators of CDI feasibility. The concept of CDI is culturally feasible in rural and semi-urban settlements, but many challenges hinder its actual implementation. In the view of community participation as a process rather than an intervention, these challenges include real dialogue with communities as partners, dialogue and advocacy with operational level health staff, and macroeconomic and political reforms in health, finance and other associated sectors. Full article

Zika virus is an emergent pathogen that gained significant importance during the epidemic in South and Central America as unusual and alarming complications of infection were recognized. Although initially considered a self-limited benign infection, a panoply of neurologic complications were recognized including a Guillain–Barré-like syndrome and in-utero fetal infection causing microcephaly, blindness, and other congenital neurologic complications. Numerous Zika virus vaccines were developed, with nine different vaccines representing five different platforms entered into clinical trials, one progressing to Phase II. Here we review the current landscape and challenges confronting Zika virus vaccine development. Full article

It is important to discover novel antimalarial pharmacophores because of the widespread emergence of Plasmodium falciparum isolates resistant to the available drugs. Secondary metabolites derived from microbes associated with marine invertebrates are a valuable resource for the discovery of novel drug leads. However, the potential of marine microbes as a source of antimalarials has not been explored. We investigated the promise of marine microorganisms for the production of antimalarial activities by testing 2365 diverse microbial extracts using phenotypic screening of a multidrug resistant chloroquine resistant P. falciparum strain. We conducted counter screening against mammalian cells for the 317 active extracts that exhibited more than 70% inhibition at 1 µg/mL. The screen identified 17 potent bioactive leads from a broad range of taxa. Our results establish that the marine microbiome is a rich source of antiplasmodial compounds that warrants in depth exploration. Full article

Evidence is emerging that shows elevated mental distress and disorder amongst people with several neglected tropical diseases (NTDs). This study aimed to establish the prevalence of depressive symptoms amongst people with podoconiosis and lower limb lymphoedema of other cause in Cameroon. The study was part of a larger research piece that mapped the geographical distribution of podoconiosis in Cameroon. The Patient Health Questionnaire (PHQ-9; mean) was employed to determine the prevalence of depressive symptoms amongst people with lower limb lymphoedema. Linear regression was used to assess the association between socio-demographic characteristics of participants and depressive symptoms. Internal consistency of the PHQ-9 was estimated through Cronbach’s alpha (α = 0.651). The mean PHQ-9 score among people with lower limb lymphoedema was 3.48 (SD ± 3.25). Using a PHQ-9 score of 5 or above as the cut-off score, 32 participants (38.6%) displayed at least mild depressive symptoms. Unemployment was the only factor that was significantly associated with more depressive symptoms overall. This study shows that depressive symptoms are common amongst people with lower limb lymphoedema in Cameroon. The findings provide support for the integration of psychosocial interventions into packages of care for the management of lower limb lymphoedema. Full article

Mosquito vectors are extending their range via international travel and trade. Climate change makes New Zealand an increasingly suitable environment for less tropically adapted exotic mosquito vectors to become established. This shift will add a multiplier effect to existing risks of both the establishment of new species and of resident exotic species extending into new areas. We describe trends in the border interceptions of exotic mosquitoes and evaluate the role of imported goods as a pathway for these introductions. Ae. aegypti and Ae. albopictus, the two most commonly intercepted species, were only intercepted in Auckland. Used tyres and machinery were the main mode of entry for both species. The majority of Ae. albopictus were transported as larvae by sea, while most Ae. aegypti were transported as adults by air. Continuing introductions of these mosquitoes, mainly arriving via Japan or Australia, increase the risk of the local transmission of mosquito-borne diseases in New Zealand in general and in the Auckland region in particular. These findings reinforce the need for a high performing and adequately resourced national biosecurity system, particularly port surveillance and inspection. Recommended biosecurity improvements are described. Full article

Uncertainty regarding transmission pathways and control measures makes prompt presentation and diagnosis for Buruli ulcer critical. To examine presentation and diagnosis delays in Victoria, Australia, we conducted a retrospective study of 703 cases notified between 2011 and 2017, classified as residing in an endemic (Mornington Peninsula; Bellarine Peninsula; South-east Bayside and Frankston) or non-endemic area. Overall median presentation delay was 30 days (IQR 14–60 days), with no significant change over the study period (p = 0.11). There were significant differences in median presentation delay between areas of residence (p = 0.02), but no significant change over the study period within any area. Overall median diagnosis delay was 10 days (IQR 0–40 days), with no significant change over the study period (p = 0.13). There were significant differences in median diagnosis delay between areas (p < 0.001), but a significant decrease over time only on the Mornington Peninsula (p < 0.001). On multivariable analysis, being aged <15 or >65 years; having non-ulcerative disease; and residing in the Bellarine Peninsula or South-East Bayside (compared to non-endemic areas) were significantly associated with shorter presentation delay. Residing in the Bellarine or Mornington Peninsula and being notified later in the study period were significantly associated with shorter diagnosis delay. To reduce presentation and diagnosis delays, awareness of Buruli ulcer must be raised with the public and medical professionals, particularly those based outside established endemic areas. Full article

A high diversity of corona- and paramyxoviruses have been detected in different bat species at study sites worldwide, including Africa, however no biosurveillance studies from Rwanda have been reported. In this study, samples from bats collected from caves in Ruhengeri, Rwanda, were tested for the presence of corona- and paramyxoviral RNA using reverse transcription PCR assays. Positive results were further characterized by DNA sequencing and phylogenetic analysis. In addition to morphological identification of bat species, we also did molecular confirmation of species identities, contributing to the known genetic database available for African bat species. We detected a novel Betacoronavirus in two Geoffroy’s horseshoe bats (Rhinolophus clivosus) bats. We also detected several different paramyxoviral species from various insectivorous bats. One of these viral species was found to be homologous to the genomes of viruses belonging to the Jeilongvirus genus. Additionally, a Henipavirus-related sequence was detected in an Egyptian rousette fruit bat (Rousettus aegyptiacus). These results expand on the known diversity of corona- and paramyxoviruses and their geographical distribution in Africa. Full article

In our previous study, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis and showed no toxic effect on L6 cells. In view of the potential use of piperidine alkaloids in S. spectabilis for the treatment of sleeping sickness, further investigation on the cell death actions of the parasite after treatment with compound 1 and 2 suggested that the treated parasites died by a process of autophagy based on the characteristic morphological alterations observed in intracellular T. b. rhodesiense. In search for apoptosis, interestingly, trypanosomes treated with high concentration of compound 1 and 2 after 72 h significantly induced an early apoptosis-like programmed cell death (PCD) such as phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and caspases activation. No DNA laddering discriminated late apoptosis event. Taken together, these findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis in T. b. rhodesiense. Full article

In February of 2016, the World Health Organization (WHO) declared Zika virus (ZIKV) a Public Health Emergency of International Concern. This prompted a rapid response from both the private and public sector resulting in the generation of several promising vaccine candidates. In this review, we discuss published scientific efforts associated with these novel vaccines, emphasizing the immunological assays used to evaluate their immunogenicity and efficacy, and support future licensure. Full article

Australia was previously believed to be free of enzootic swine influenza viruses due strict quarantine practices and use of biosecure breeding facilities. The first proven Australian outbreak of swine influenza occurred in Western Australian in 2012, revealing an unrecognized zoonotic risk, and a potential future pandemic threat. A public health investigation was undertaken to determine whether zoonotic infections had occurred and to reduce the risk of further transmission between humans and swine. A program of monitoring, testing, treatment, and vaccination was commenced, and a serosurvey of workers was also undertaken. No acute infections with the swine influenza viruses were detected. Serosurvey results were difficult to interpret due to previous influenza infections and past and current vaccinations. However, several workers had elevated haemagglutination inhibition (HI) antibody levels to the swine influenza viruses that could not be attributed to vaccination or infection with contemporaneous seasonal influenza A viruses. However, we lacked a suitable control population, so this was inconclusive. The experience was valuable in developing better protocols for managing outbreaks at the human–animal interface. Strict adherence to biosecurity practices, and ongoing monitoring of swine and their human contacts is important to mitigate pandemic risk. Strain specific serological assays would greatly assist in identifying zoonotic transmission. Full article

Arboviruses are viruses transmitted to humans by the bite of infected mosquito vectors. Over the last decade, arbovirus circulation has increasingly been detected in New Caledonia (NC), a French island territory located in the subtropical Pacific region. Reliable epidemiological, entomological, virological and climate data have been collected in NC over the last decade. Here, we describe these data and how they inform arboviruses’ epidemiological profile. We pinpoint areas which remain to be investigated to fully understand the peculiar epidemiological profile of arbovirus circulation in NC. Further, we discuss the advantages of conducting studies on arboviruses dynamics in NC. Overall, we show that conclusions drawn from observations conducted in NC may inform epidemiological risk assessments elsewhere and may be vital to guide surveillance and response, both in New Caledonia and beyond. Full article

The End Tuberculosis (TB) Strategy has the ambitious goal of ending the global TB epidemic by the year 2030, which is aligned to the Sustainable Development Goals. One of three high level indicators of the Strategy is the “catastrophic costs” indicator, which aims to determine the proportion of TB-affected households that incur TB-care related costs equivalent to 20% or more of their annual household income. The target is that zero percentage of TB-affected households will incur catastrophic costs related to TB care by the year 2020. In the Western Pacific Region of the World Health Organization, it is a priority to determine the financial burden of TB and then act to mitigate it. To date, eight countries in the Region have conducted nationally representative TB patient cost surveys to determine the costs of TB care. The results from four countries that have completed these surveys (i.e., Fiji, Mongolia, the Philippines, and Vietnam) indicate that between 35% and 70% of TB patients face catastrophic costs related to their TB care. With these results in mind, significant additional efforts are needed to ensure financial risk protection for TB patients, expand Universal Health Coverage, and improve access to social protection interventions. A multi-sectoral approach is necessary to achieve this ambitious goal by the year 2020. Full article

Soil-transmitted helminth (STH) infections are globally distributed intestinal parasite infections caused by Ascaris lumbricoides, Trichuris trichiura, and hookworms (Ancylostoma duodenale and Necator americanus). STH infection constitutes a major public health threat, with heavy burdens observed in many of the world’s tropical and subtropical regions. Mass drug administration and sanitation improvements can drastically reduce STH prevalence and associated morbidity. However, identifying targeted areas in need of treatment is hampered by a lack of knowledge on geographical and population-level risk factors. In this study, we applied Bayesian geostatistical modelling to data from a national school-based STH infection survey in Rwanda to (1) identify ecological and population-level risk factors and (2) provide comprehensive precision maps of infection burdens. Our results indicated that STH infections were heterogeneously distributed across the country and showed signatures of spatial clustering, though the magnitude of clustering varied among parasites. The highest rates of endemic clustering were attributed to A. lumbricoides infection. Concordant infection patterns among the three parasite groups highlighted populations currently most at-risk of morbidity. Population-dense areas in the Western and North-Western regions of Rwanda represent areas that have continued to exhibit high STH burden across two surveys and are likely in need of targeted interventions. Our maps support the need for an updated evaluation of STH endemicity in western Rwanda to evaluate progress in MDA efforts and identify communities that need further local interventions to further reduce morbidity caused by STH infections. Full article

Here, we review all data available at the Ministry of Public Health in order to describe the history of the National Program for Onchocerciasis Control (NPOC) in the Democratic Republic of the Congo (DRC). Discovered in 1903, the disease is endemic in all provinces. Ivermectin was introduced in 1987 as clinical treatment, then as mass treatment in 1989. Created in 1996, the NPOC is based on community-directed treatment with ivermectin (CDTI). In 1999, rapid epidemiological mapping for onchocerciasis surveys were launched to determine the mass treatment areas called “CDTI Projects”. CDTI started in 2001 and certain projects were stopped in 2005 following the occurrence of serious adverse events. Surveys coupled with rapid assessment procedures for loiasis and onchocerciasis rapid epidemiological assessment were launched to identify the areas of treatment for onchocerciasis and loiasis. In 2006, CDTI began again until closure of the activities of African Program for Onchocerciasis Control (APOC) in 2015. In 2016, the National Program for Neglected Tropical Diseases Control using Preventive Chemotherapy (PNMTN-CP) was launched to replace NPOC. Onchocerciasis and CDTI are little known by the population. The objective of eliminating onchocerciasis by 2025 will not be achieved due to the poor results of the NPOC. The reform of strategies for eliminating this disease is strongly recommended. Full article

The 1918 influenza pandemic was the most significant pandemic recorded in human history. Worldwide, an estimated half billion persons were infected and 20 to 100 million people died in three waves during 1918 to 1919. Yet the impact of this pandemic has been poorly documented in many countries especially those in Africa. We used colonial-era records to describe the impact of 1918 influenza pandemic in the Coast Province of Kenya. We gathered quantitative data on facility use and all-cause mortality from 1912 to 1925, and pandemic-specific data from active reporting from September 1918 to March 1919. We also extracted quotes from correspondence to complement the quantitative data and describe the societal impact of the pandemic. We found that crude mortality rates and healthcare utilization increased six- and three-fold, respectively, in 1918, and estimated a pandemic mortality rate of 25.3 deaths/1000 people/year. Impact to society and the health care system was dramatic as evidenced by correspondence. In conclusion, the 1918 pandemic profoundly affected Coastal Kenya. Preparation for the next pandemic requires continued improvement in surveillance, education about influenza vaccines, and efforts to prevent, detect and respond to novel influenza outbreaks. Full article

Pregnant women are significantly more likely to have an asymptomatic acute infection with C. burnetii which, untreated, has been associated with poor obstetric outcomes including miscarriage, stillbirth, intrauterine growth restriction, and premature delivery. As such, Q fever is a potentially under-recognised and treatable cause of adverse pregnancy outcomes in rural Northern New South Wales, with testing of Q fever polymerase chain reaction (PCR)—whether on maternal sera or placental tissue—not currently recommended by the Perinatal Society of Australia and New Zealand for Stillbirth. Full article