Soil-transmitted helminths (STHs) pose significant public health challenges in many countries of Southeast Asia (SEA). Overall, approximately one-third of the world's cases of ascariasis, trichuriasis, and hookworm disease occur in the 11 major SEA countries. Various countries are at different stages in their response to controlling these diseases. For instance, in Malaysia and Thailand, the major burden of disease is confined to rural/remote, indigenous and/or refugee populations. In countries, such as Cambodia, Lao People's Democratic Republic and Vietnam, the burden remains high, although extensive deworming programmes are underway and are yielding encouraging results. The present chapter reviews the current status of STH infections in SEA, identifies knowledge gaps and offers a perspective on the development of improved, integrated surveillance and control in this geographical region. It indicates that advances in our understanding of the epidemiology of these parasites, through the strategic use of molecular and predictive (e.g. geographical information systems (GIS) and remote sensing (RS)) technologies, could readily underpin future research and control programmes. It is hoped that the gradual move towards integrated treatment/control programmes will assist substantially in decreasing the chronic disease burden linked to STHs, thus increasing human health and welfare, and supporting socio-economic growth and development in SEA countries.
Ethnic minority groups (EMGs) are often subject to exclusion, marginalization and poverty. These characteristics render them particularly vulnerable to neglected diseases, a diverse group of diseases that comprise bacteria, ecto-parasites, fungi, helminths and viruses. Despite the health policy relevance, only little is known of the epidemiological profile of neglected diseases among EMGs. We reviewed country data from Australia, Cambodia, Lao People's Democratic Republic, Malaysia, the Philippines and Vietnam and found several overlaps between regions with high proportions of EMG population and high prevalence rates of neglected diseases (infections with soil-transmitted helminths, filarial worms, schistosomes, food-borne trematodes and cestodes). While the links are not always clearly evident and it is impossible to establish correlations among highly aggregated data without control variables-such as environmental factors-there appear indeed to be important linkages between EMGs, socio-economic status and prevalence of neglected diseases. Some determinants under consideration are lack of access to health care and general health status, poverty and social marginalization, as well as education and literacy. Further research is needed to deepen the understanding of these linkages and to determine their public health and socio-economic significance. In particular, there is a need for more data from all countries in the Western Pacific Region that is disaggregated below the provincial level. Selected case studies that incorporate other control variables-such as risk factors from the physical environment-might be useful to inform policy makers about the feasibility of prevention and control interventions that are targeted at high-risk EMGs.
Toxocariasis is a human infection primarily caused by larvae of Toxocara canis from dogs, and also by T. cati from cats. Children have a more significant risk of acquiring the infection due to their closer contact with pets, and greater chances of ingesting soil. Diagnosis of toxocariasis is based on clinical, epidemiological, and serological data. Indirect IgG ELISA is a widely used serodiagnostic method for toxocariasis, with native T. canis TES most commonly used as the antigen. Western blots, using the same antigen, can be used to confirm positive ELISA findings to reduce false-positive results. Improvements in Toxocara serodiagnosis include the use of recombinant TES antigens, simpler and more rapid assay formats, and IgG4 subclass detection. Also, incorporation of recombinant T. cati TES protein increases the diagnostic sensitivity. Development of antigen detection tests using polyclonal and monoclonal antibodies, nanobodies, or aptamers can complement the antibody detection assays, and enhance the effectiveness of the serodiagnosis.
Within the overlapping geographical ranges of P. knowlesi monkey hosts and vectors in Southeast Asia, an estimated 1.5 billion people are considered at risk of infection. P. knowlesi can cause severe disease and death, the latter associated with delayed treatment occurring from misdiagnosis. Although microscopy is a sufficiently sensitive first-line tool for P. knowlesi detection for most low-level symptomatic infections, misdiagnosis as other Plasmodium species is common, and the majority of asymptomatic infections remain undetected. Current point-of-care rapid diagnostic tests demonstrate insufficient sensitivity and poor specificity for differentiating P. knowlesi from other Plasmodium species. Molecular tools including nested, real-time, and single-step PCR, and loop-mediated isothermal amplification (LAMP), are sensitive for P. knowlesi detection. However, higher cost and inability to provide the timely point-of-care diagnosis needed to guide appropriate clinical management has limited their routine use in most endemic clinical settings. P. knowlesi is likely underdiagnosed across the region, and improved diagnostic and surveillance tools are required. Reference laboratory molecular testing of malaria cases for both zoonotic and non-zoonotic Plasmodium species needs to be more widely implemented by National Malaria Control Programs across Southeast Asia to accurately identify the burden of zoonotic malaria and more precisely monitor the success of human-only malaria elimination programs. The implementation of specific serological tools for P. knowlesi would assist in determining the prevalence and distribution of asymptomatic and submicroscopic infections, the absence of transmission in certain areas, and associations with underlying land use change for future spatially targeted interventions.
The zoonotic parasite Plasmodium knowlesi has emerged as an important cause of human malaria in parts of Southeast Asia. The parasite is indistinguishable by microscopy from the more benign P. malariae, but can result in high parasitaemias with multiorgan failure, and deaths have been reported. Recognition of severe knowlesi malaria, and prompt initiation of effective therapy is therefore essential to prevent adverse outcomes. Here we review all studies reporting treatment of uncomplicated and severe knowlesi malaria. We report that although chloroquine is effective for the treatment of uncomplicated knowlesi malaria, artemisinin combination treatment is associated with faster parasite clearance times and lower rates of anaemia during follow-up, and should be considered the treatment of choice, particularly given the risk of administering chloroquine to drug-resistant P. vivax or P. falciparum misdiagnosed as P. knowlesi malaria in co-endemic areas. For severe knowlesi malaria, intravenous artesunate has been shown to be highly effective and associated with reduced case-fatality rates, and should be commenced without delay. Regular paracetamol may also be considered for patients with severe knowlesi malaria or for those with acute kidney injury, to attenuate the renal damage resulting from haemolysis-induced lipid peroxidation.
Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use change. With a 24-h asexual life cycle in humans, high parasite counts are possible, but most clinical cases of knowlesi malaria are uncomplicated with low parasitaemia. In co-endemic areas, median parasitaemia in knowlesi malaria is lower than that seen in vivax and falciparum malaria, suggesting a lower fever threshold. Severe malaria occurs in 6-9% of symptomatic adults. Manifestations of severe malaria from P. knowlesi are similar to those seen with falciparum malaria, with the notable absence of coma. Age, parasitaemia, cardiovascular comorbidities and delayed diagnosis are risk factors for severe disease and death, which are only seen in adults. Thrombocytopenia is near-universal in adults, likely related to platelet-red cell binding and clearance. Mechanisms underlying the microvascular sludging seen in fatal disease in non-natural primate hosts and the microvascular accumulation of parasites in fatal human disease are not clear. Marked reductions in deformability of both infected and uninfected red blood cells are associated with disease severity in both humans and other non-natural primate hosts, likely contributing to impaired microvascular perfusion and organ dysfunction. Endothelial activation, endothelial dysfunction, glycocalyx degradation and haemolysis are also associated with, and likely contribute to, severe disease and organ dysfunction, particularly acute kidney injury.
Plasmodium knowlesi, a simian malaria parasite of great public health concern has been reported from most countries in Southeast Asia and exported to various countries around the world. Currently P. knowlesi is the predominant species infecting humans in Malaysia. Besides this species, other simian malaria parasites such as P. cynomolgi and P. inui are also infecting humans in the region. The vectors of P. knowlesi and other Asian simian malarias belong to the Leucosphyrus Group of Anopheles mosquitoes which are generally forest dwelling species. Continual deforestation has resulted in these species moving into forest fringes, farms, plantations and human settlements along with their macaque hosts. Limited studies have shown that mosquito vectors are attracted to both humans and macaque hosts, preferring to bite outdoors and in the early part of the night. We here review the current status of simian malaria vectors and their parasites, knowledge of vector competence from experimental infections and discuss possible vector control measures. The challenges encountered in simian malaria elimination are also discussed. We highlight key knowledge gaps on vector distribution and ecology that may impede effective control strategies.
Within the past two decades, incidence of human cases of the zoonotic malaria Plasmodium knowlesi has increased markedly. P. knowlesi is now the most common cause of human malaria in Malaysia and threatens to undermine malaria control programmes across Southeast Asia. The emergence of zoonotic malaria corresponds to a period of rapid deforestation within this region. These environmental changes impact the distribution and behaviour of the simian hosts, mosquito vector species and human populations, creating new opportunities for P. knowlesi transmission. Here, we review how landscape changes can drive zoonotic disease emergence, examine the extent and causes of these changes across Southeast and identify how these mechanisms may be impacting P. knowlesi dynamics. We review the current spatial epidemiology of reported P. knowlesi infections in people and assess how these demographic and environmental changes may lead to changes in transmission patterns. Finally, we identify opportunities to improve P. knowlesi surveillance and develop targeted ecological interventions within these landscapes.
Molecular epidemiology has been central to uncovering P. knowlesi as an important cause of human malaria in Southeast Asia, and to understanding the complex nature of this zoonosis. Species-specific parasite detection and characterization of sequences were vital to show that P. knowlesi was distinct from the human parasite species that had been presumed to cause all malaria. With established sensitive and specific molecular detection tools, surveys subsequently indicated the distribution of P. knowlesi infections in humans, wild primate reservoir host species, and mosquito vector species. The importance of studying P. knowlesi genetic polymorphism was indicated initially by analysing a few nuclear gene loci as well as the mitochondrial genome, and subsequently by multi-locus microsatellite analyses and whole-genome sequencing. Different human infections generally have unrelated P. knowlesi genotypes, acquired from the diverse local parasite reservoirs in macaques. However, individual human infections are usually less genetically complex than those of wild macaques which experience more frequent superinfection with different P. knowlesi genotypes. Multi-locus analyses have revealed deep population subdivisions within P. knowlesi, which are structured both geographically and in relation to different macaque reservoir host species. Simplified genotypic discrimination assays now enable efficient large-scale surveillance of the sympatric P. knowlesi subpopulations within Malaysian Borneo. The whole-genome sequence analyses have also identified loci under recent positive natural selection in the P. knowlesi genome, with evidence that different loci are affected in different populations. These provide a foundation to understand recent adaptation of the zoonotic parasite populations, and to track and interpret future changes as they emerge.