Imunização contra malária: perspectivas e desafios / Malaria immunization: prospects and challenges

O referido trabalho tem como objetivo analisar e avaliar a atual conjuntura das pesquisas científicas na busca da imunização eficaz contra a malária, destacando os principais mecanismos imunológicos e moleculares subjacentes à referida proteção, bem como, as perspectivas a curto e médio prazo. O presente estudo de revisão selecionou pesquisas nas bases de dados da Medical Literature Analysis and Retrieval System Online (Medline), National Library of Medicine (Pubmed), Scientific Electronic Library Online (SciELO), Web of Science e Scopus. Foram combinados os termos Malaria, Immunization, Vaccine and Epidemiology, com seus sinônimos remissivos e outros descritores associados, no período compreendido entre janeiro e julho de 2019. Como fator preponderante dos critérios de inclusão, foram selecionadas revisões sistemáticas com ou sem metanálise, publicadas nos últimos 5 anos, que discorressem detalhadamente sobre o tema, ou que apresentassem informações estatísticas ou históricas relevantes, relacionada ao tema. Como critérios de exclusão foram considerados: materiais literários e científicos, anteriores ao período de 2014 e que não apresentassem informações estatísticas ou histórica relevantes ao tema, ou que, não se adequassem à temática da pesquisa. Após a aplicação dos critérios de inclusão e exclusão, foi realizada a análise e seleção dos artigos. Dos 451 artigos identificados, 44 foram selecionados. As informações extraídas dos referidos trabalhos convergem no sentido de que a erradicação da malária é uma tarefa demasiadamente complexa, a qual não será alcançada com as vacinas atuais, havendo necessidade do desenvolvimento de ferramentas imunizadoras de maior eficácia. Apesar dos esforços, atualmente ainda não existe uma vacina eficaz na prevenção da infecção, mas vários estudos se encontram em andamento nessa vertente, tornando promissor o surgimento de uma vacina eficaz contra o parasita.

This study aims at analyzing and evaluating the current status of scientific research in the search for effective immunization against malaria, highlighting the key immunological and molecular mechanisms of such protection and the short- and medium-term perspectives. The search and selection of studies took place in the databases of the Medical Literature Analysis and Retrieval System Online (Medline); National Library of Medicine (Pubmed); Scientific Electronic Library Online (SciELO); Web of Science; and Scopus. The terms Malaria, Immunization, Vaccine, and Epidemiology were used, with their corresponding cross-referenced synonyms and other associated descriptors, including the period from January to July 2019. As a main factor in the inclusion criteria, systematic reviews with or without meta-analysis published in the last 5 years, presenting a detailed discourse about the topic, or relevant statistical or historical information related to the topic were selected. The following exclusion criteria were considered: literary and scientific materials, prior to 2014, and without statistical or historical information relevant to the theme, or which did not fit the research theme. After applying the inclusion and exclusion criteria, the articles were analyzed and selected. From a total of 451 identified articles, 44 were selected. The information extracted from the referred studies converge in the sense that malaria eradication is an overly complex task, which will not be achieved with the current vaccines, requiring the development of more effective immunizing tools. Despite all the efforts, there is no effective vaccine for preventing infection yet, but several studies are being developed in this area, making the emergence of an effective vaccine against the disease promising.

Host-parasite interactions in vector-borne protozoan infections.

Protists embrace many species, some of which may be either occasional or permanent parasites of vertebrate animals. Between the parasite species, several of medical and veterinary importance are vector-transmitted. The ecology and epidemiology of vector-borne parasitoses, including babesiosis, leishmaniasis and malaria, are particularly complex, as they are influenced by many factors, such as vector reproductive efficiency and geographical spread, vectorial capacity, host immunity, travel and human behaviour and climatic factors. Transmission dynamics are determined by the interactions between pathogen, vector, host and environmental factors and, given their complexity, many different types of mathematical models have been developed to understand them. A good basic knowledge of vector-pathogen relationships and transmission dynamics is thus essential for disease surveillance and control interventions and may help in understanding the spread of epidemics and be useful for public health planning.

Non-specific effects of BCG in protozoal infections: tegumentary leishmaniasis and malaria.

BACKGROUND: Leishmaniasis and malaria are major causes of illness in the poorest countries. In the absence of efficient strategies to prevent infections and to control the transmission of the parasites by insect vectors, treatment relies on drug therapy. Vaccine development continues on several fronts; however none of the candidates developed has so far been shown to provide long-lasting protection at a population level. Because the bacillus Calmette-Guérin (BCG) vaccine can induce heterologous protective effects, we hypothesize that BCG has beneficial effects in the control of tegumentary leishmaniasis (TL) and malaria. AIMS: In this review we describe evidence for the protective efficacy of BCG against tegumentary leishmaniasis and malaria in humans. SOURCES: Relevant data from peer-reviewed scientific literature published on Pubmed up to January 2019 were examined. CONTENT: From experimental animal and various human studies with BCG and one recent randomized malaria trial there is evidence that BCG has beneficial effects in Leishmania spp. and Plasmodium falciparum infections. Although the precise mechanisms remain unknown, BCG can activate innate immune responses, and an increasing body of evidence demonstrates that the induction of trained innate immunity could explain its non-specific protective effects. IMPLICATIONS: Despite many years of research to prevent and treat TL and malaria, these diseases remain a public health problem in tropical countries. Future studies are required to examine if BCG vaccination could be used as an effective treatment option.

International survey on the impact of parasitic infections: frequency of transmission and current mitigation strategies.

BACKGROUND AND OBJECTIVES: Globally, blood safety interventions have been successful in mitigating risk of the major transfusion-transmitted (TT) viruses. However, strategies that address risk from parasites are comparatively limited. TT parasites are often regional in nature, posing unique challenges; we sought to understand their impact on blood safety. MATERIALS AND METHODS: An electronic questionnaire was distributed to transfusion medicine leaders in 100 countries. The survey focused on specific questions pertaining to four parasitic diseases: babesiosis, Chagas, leishmaniasis and malaria. Respondents provided data on historical TT cases, local epidemiology, policies to mitigate risk and an assessment of public health perceptions for each aetiologic agent. RESULTS: Twenty-eight (28%) surveys were returned from countries in Europe (n = 13), the Americas (n = 6), Africa (n = 4), Asia (n = 3) and Oceana (n = 2). Historically, no cases of TT leishmaniasis were reported, TT babesiosis was exclusive to Canada and the USA, TT Chagas was limited to the Americas and Spain, while TT malaria was cosmopolitan. Mitigation efforts varied widely; malaria was the most frequently tested parasitic disease. The public's perception of risk for parasitic agents was low, while that of health authorities in endemic countries was higher. CONCLUSION: The global impact of parasitic infections on blood safety and related mitigation efforts varied widely by parasite epidemiology, test availability, public health priorities and socioeconomic constraints. While parasites continue to pose a risk to blood safety, the successful mitigation of viral risk has elevated the prominence of TT parasites in many locations, thereby requiring consideration of mitigation efforts.

Vigilancia de paludismo en Argentina: 2005-2018 / Malaria surveillance in Argentina: 2005-2018

El paludismo o malaria es una enfermedad potencialmente mortal causada por la infección de una o más de cinco especies de parásitos protozoarios intracelulares: Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae, y Plasmodium knowlesi, que se transmiten al ser humano por la picadura de mosquitos hembra infectados del género Anopheles. Se describen antecedentes, situación actual, casos notificados en Argentina, estratificación de riesgo de reintroducción de paludismo en el país, definición de casos sospechosos y confirmados, y acciones epidemiológicas realizadas

Recombinant helical plant virus-based nanoparticles for vaccination and immunotherapy.

Plant virus-based nanoparticles (PVNs) are self-assembled capsid proteins of plant viruses, and can be virus-like nanoparticles (VLPs) or virus nanoparticles (VNPs). Plant viruses showing helical capsid symmetry are used as a versatile platform for the presentation of multiple copies of well-arrayed immunogenic antigens of various disease pathogens. Helical PVNs are non-infectious, biocompatible, and naturally immunogenic, and thus, they are suitable antigen carriers for vaccine production and can trigger humoral and/or cellular immune responses. Furthermore, recombinant PVNs as vaccines and adjuvants can be expressed in prokaryotic and eukaryotic systems, and plant expression systems can be used to produce cost-effective antigenic peptides on the surfaces of recombinant helical PVNs. This review discusses various recombinant helical PVNs based on different plant viral capsid shells that have been developed as prophylactic and/or therapeutic vaccines against bacterial, viral, and protozoal diseases, and cancer.

Allocation of Interferon Gamma mRNA Positive Cells in Caecum Hallmarks a Protective Trait Against Histomonosis.

Histomonosis is a parasitic disease of gallinaceous birds characterized by necrotic lesions in cacum and liver that usually turns fatal in turkeys while it is less severe in chickens. Vaccination using in vitro attenuated Histomonas meleagridis has been experimentally shown to confer protection against histomonosis. The protective mechanisms that underpin the vaccine-induced immune response are not resolved so far. Therefore, the actual study aimed to evaluate the location and quantitative distribution patterns of signature cytokines of type 1 [interferon gamma (IFN-γ)] or type 2 [interleukin (IL)-13] immune responses in vaccinated or infected hosts. An intergroup and interspecies difference in the spatial and temporal distribution patterns of cytokine mRNA positive cells was evident. Quantification of cells showed a significantly decreased percentage of IFN-γ mRNA positive cells at 4 days post-inoculation (DPI) in caeca of turkeys inoculated exclusively with the attenuated or the virulent inocula, compared to control birds. The decrement was followed by a surge of cells expressing mRNA for IFN-γ or IL-13, reaching a peak of increment at 10 DPI. By contrast, turkeys challenged following vaccination showed a slight increment of cecal IFN-γ mRNA positive cells at 4 DPI after which positive cell counts became comparable to control birds. The increase in infected birds was accompanied by an extensive distribution of positively stained cells up to the muscularis layer of cecal tissue whereas the vaccine group maintained an intact mucosal structure. In chickens, the level of changes of positive cells was generally lower compared to turkeys. However, control chickens were found with a higher percentage of IFN-γ mRNA positive cells in cecum compared to their turkey counterparts indicating a higher resistance to histomonosis, similar to the observation in immunized turkeys. In chickens, it could be shown that the changes of cytokine-positive cells were related to variations of mononuclear cells quantified by immunofluorescence. Furthermore, gene expression measured by reverse transcription quantitative real time PCR confirmed variations in organs between the different groups of both bird species. Overall, it can be concluded that a proportionally increased, yet controlled, allocation of IFN-γ mRNA positive cells in caeca hallmarks a protective trait against histomonosis.

Effect of an integrated intervention package of preventive chemotherapy, community-led total sanitation and health education on the prevalence of helminth and intestinal protozoa infections in Côte d'Ivoire.

BACKGROUND: Preventive chemotherapy with donated anthelminthic drugs is the cornerstone for the control of helminthiases. However, reinfection can occur rapidly in the absence of clean water and sanitation coupled with unhygienic behaviour. The purpose of this study was to assess the effect of an integrated package of interventions, consisting of preventive chemotherapy, community-led total sanitation (CLTS) and health education, on the prevalence of helminth and intestinal protozoa infections and on participants' knowledge, attitude, practice and beliefs (KAPB) towards these diseases including water, sanitation and hygiene (WASH). METHODS: A cross-sectional survey was carried out in nine communities of south-central Côte d'Ivoire to assess people's infection with helminths and intestinal protozoa and KAPB. Subsequently, interventions were targeted to five communities, while the remaining communities served as control. The intervention encouraged latrine construction and an evaluation was done 6-7 months later to determine open defecation status of the respective communities. Anthelminthic treatment was provided to all community members. A follow-up cross-sectional survey was conducted approximately one year later, using the same procedures. RESULTS: Overall, 810 people had complete baseline and follow-up data and were given anthelminthic treatment. The baseline prevalence of hookworm, Schistosoma haematobium, Trichuris trichiura, Schistosoma mansoni and Ascaris lumbricoides was 31.1%, 7.0%, 2.0%, 1.0% and 0.3%, respectively. Four of the five intervention communities were classified open-defecation free. For hookworm infection, we observed higher negative changes in terms of proportion of decrease (-0.10; 95% confidence interval (CI): - 0.16, -0.04) and higher egg reduction rate (64.9 vs 15.2%) when comparing intervention with control communities. For intestinal protozoa, prevalence reduction was higher in intervention compared to control communities (8.2 vs 2.6%) and WASH indicators and intervention outcomes associated with lower odds for infection at follow-up. The intervention significantly impacted on reported latrine use (before: 15.5%, after: 94.6%), open defecation in the community surroundings (before: 75.0%, after: 16.7%) and awareness for environmental contamination through open defecation (before: 20.4%, after: 52.2%). CONCLUSIONS: An integrated package of interventions consisting of preventive chemotherapy, health education and CLTS reduces the prevalence of helminth and intestinal protozoa infection. Additional studies in other social-ecological settings are warranted to confirm our findings.

Homeopathic treatment as an alternative prophylactic to minimize bacterial infection and prevent neonatal diarrhea in calves.

Bovine neonatal diarrhea is common due low immunity in newborn calves, poor management (or absence) of sanitary barriers, and other factors. Newborn calves with diarrhea in the first days of life suffer failure to thrive and may die if left untreated. The aim of this study was to evaluate whether prophylactic administration of a homeopathic product (Dia 100®) can control bovine neonatal diarrhea in calves born on a farm with substantial sanitary challenges. We counted total bacteria and protozoan parasites in fecal samples. We measured serum glucose, total protein, globulin, albumin, cholesterol and triglycerides on days 1, 7 and 14 of life. Twenty newborn calves were maintained in individual stalls, and were divided in two groups: ten untreated animals (control) and ten animals treated with Dia 100®. Fecal consistency was evaluated daily. We diagnosed diarrhea in five animals in the treated group, and in all animals from the control group. Infections with Escherichia coli and Giardia duodenalis were identified as the responsible organisms. The E. coli count was low in the treatment group on day 7 of life compared with the control group. Antibiotics were given to eight animals in the control group, and to two animals in the treatment group. On day of life 7, serum levels of total protein and globulins were higher in the control group, but were lower on day 14. Serum levels of glucose and triglycerides were greater in treated animals on days 7 and 14, suggesting that the homeopathic product contributes to improvement of intestinal health and absorption and nutrients. We conclude that Dia 100® controls diarrhea with 50% of efficacy, and reduces antibiotic utilization.

Contribution of in Vivo Experimental Challenges to Understanding Flat Oyster Ostrea edulis Resistance to Bonamia ostreae.

Bonamiosis due to the parasite Bonamia ostreae has been associated with massive mortality outbreaks in European flat oyster stocks in Europe. As eradication and treatment are not possible, the control of the disease mainly relies on transfer restriction. Moreover, selection has been applied to produce resistant flat oyster families, which present better survival and lower prevalence than non-selected oysters. In order to better understand the mechanisms involved in resistance to bonamiosis, cellular and molecular responses of 2 oyster groups (selected oysters and wild-type oysters) were analyzed in the context of experimental injection and cohabitation infections. Cellular responses including non-specific esterases detection, ROS production and phagocytosis activity were analyzed by flow cytometry. Four genes homologous to those shown to be involved in immunity were selected (Inhibitor of apotosis OeIAP, Fas ligand OeFas-ligand, Oe-SOD, and OeEc-SOD) and monitored by quantitative reverse-transcription PCR (qRT-PCR). Infected oysters showed higher phagocytosis activity than controls. Infected selected oyster show a lower phagocytosis activity which might be a protection against the parasite infection. The expression of OeIAP and OeFas-ligand gene was significantly increased in selected oysters at 5 days post-injection. OeIAP gene expression appeared to be significantly increased in wild-type oysters at 8 days post-injection. Our results suggest that resistance to bonamiosis partly relies on the ability of the oysters to modulate apoptosis.

Vaccination against histomonosis limits pronounced changes of B cells and T-cell subsets in turkeys and chickens.

The protozoan parasite Histomonas meleagridis is the causative agent of histomonosis in gallinaceous birds. In turkeys, the disease can result in high mortality due to severe inflammation and necrosis in caecum and liver, whereas in chickens the disease is less severe. Recently, experimental vaccination was shown to protect chickens and turkeys against histomonosis but dynamics in the cellular immune response are not yet demonstrated. In the present work, different groups of birds of both species were vaccinated with attenuated, and/or infected with virulent histomonads. Flow cytometry was applied at different days post inoculation to analyse the absolute number of T-cell subsets and B cells in caecum, liver, spleen and blood, in order to monitor changes in these major lymphocyte subsets. In addition, in chicken samples total white blood cells were investigated. Infected turkeys showed a significant decrease of T cells in the caecum within one week post infection compared to control birds, whereas vaccination showed delayed changes. The challenge of vaccinated turkeys led to a significant increase of all investigated lymphocytes in the blood already at 4 DPI, indicating an effective and fast recall response of the primed immune system. In the caecum of chickens, changes of B cells, CD4+ and CD8α+ T cells were much less pronounced than in turkeys, however, mostly caused by virulent histomonads. Analyses of whole blood in non-vaccinated but infected chickens revealed increasing numbers of monocytes/macrophages on all sampling days, whereas a decrease of heterophils was observed directly after challenge, suggesting recruitment of this cell population to the local site of infection. Our results showed that virulent histomonads caused more severe changes in the distribution of lymphocyte subsets in turkeys compared to chickens. Moreover, vaccination with attenuated histomonads resulted in less pronounced alterations in both species, even after challenge.

Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases.

Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required. The majority of current therapeutic trypanosomatid targets are enzymes or cell-surface receptors. Among these, eukaryotic protein kinases are a major group of protein targets whose modulation may be beneficial for the treatment of neglected tropical protozoan diseases. This review summarizes the finding of new hit compounds for neglected tropical protozoan diseases, by repurposing known human kinase inhibitors on trypanosomatids. Kinase inhibitors are grouped by human kinase family and discussed according to the screening (target-based or phenotypic) reported for these compounds on trypanosomatids. This collection aims to provide insight into repurposed human kinase inhibitors and their importance in the development of new chemical entities with potential beneficial effects on the diseases caused by trypanosomatids.

Household sanitation is associated with lower risk of bacterial and protozoal enteric infections, but not viral infections and diarrhoea, in a cohort study in a low-income urban neighbourhood in Vellore, India.

OBJECTIVE: This study examined associations between household sanitation and enteric infection - including diarrhoeal-specific outcomes - in children 0-2 years of age in a low-income, dense urban neighbourhood. METHODS: As part of the MAL-ED study, 230 children in a low-income, urban, Indian neighbourhood provided stool specimens at 14-17 scheduled time points and during diarrhoeal episodes in the first 2 years of life that were analysed for bacterial, parasitic (protozoa and helminths) and viral pathogens. From interviews with caregivers in 100 households, the relationship between the presence (and discharge) of household sanitation facilities and any, pathogen-specific, and diarrhoea-specific enteric infection was tested through mixed-effects Poisson regression models. RESULTS: Few study households (33%) reported having toilets, most of which (82%) discharged into open drains. Controlling for season and household socio-economic status, the presence of a household toilet was associated with lower risks of enteric infection (RR: 0.91, 95% CI: 0.79-1.06), bacterial infection (RR: 0.87, 95% CI: 0.75-1.02) and protozoal infection (RR: 0.64, 95% CI: 0.39-1.04), although not statistically significant, but had no association with diarrhoea (RR: 1.00, 95% CI: 0.68-1.45) or viral infections (RR: 1.12, 95% CI: 0.79-1.60). Models also suggested that the relationship between household toilets discharging to drains and enteric infection risk may vary by season. CONCLUSIONS: The presence of a household toilet was associated with lower risk of bacterial and protozoal enteric infections, but not diarrhoea or viral infections, suggesting the health effects of sanitation may be more accurately estimated using outcome measures that account for aetiologic agents.

Occurrence of Cryptosporidium and Giardia and the Relationship between Protozoa and Water Quality Indicators in Swimming Pools.

A total of 60 samples were collected from 35 swimming pools in Beijing, China, and the presence of Cryptosporidium and Giardia were investigated. The results showed that 16.7% and 15.0% of samples were positive for Cryptosporidium oocyst and Giardia cysts, respectively, with a mean concentration of 0.30 oocysts/10 L and 0.27 cysts/10 L. The oocysts and cysts were found to have higher rates of occurrence in August than in May. Genotyping confirmed the presence of Cryptosporidium hominis, C. parvum, and Giardia assemblages A and B, all of which were associated with human infections. The predominant species/assemblages were C. hominis and Giardia assemblage A. Analyses of the relationships between parasite oocysts/cysts, indicator bacteria, and physical-chemical parameters revealed that there was no correlation between 2 parasites and fecal bacterial indicators, whilst there was a significant correlation between protozoa and urea concentration, which indicates that urea concentration rather than fecal bacterial indicators might be an appropriate index for chlorine-resistant protozoa in swimming pools. This study provides useful information to improve the safety of swimming pool water and deduce the risk of protozoan infections.

Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.

Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors.

Pathogen-induced secretory diarrhea and its prevention.

Secretory diarrhea is a historically known serious health implication around the world which primarily originates through pathogenic microorganisms rather than immunological or genetical disorders. This review highlights infective mechanisms of non-inflammatory secretory diarrhea causing pathogens, known therapeutics and their efficacy against them. These non-inflammatory diarrheal pathogens breach cell barriers, induce inflammation, disrupt fluid secretion across the epithelium by alteration in ion transport by faulting cystic fibrosis transmembrane conductance regulator (CFTR), calcium activated chloride channels and ion exchanger functions. Currently, a variety of prevention strategies have been used to treat these symptoms like use of antibacterial drugs, vaccines, fluid and nutritional therapy, probiotics and prebiotics as adjuncts. In progression of the need for a therapy having quick physiological effects, withdrawing the symptoms with a wide and safe therapeutic index, newer antisecretory agents like potent inhibitors, agonists and herbal remedies are some of the interventions which have come into light through greater understanding of the mechanisms and molecular targets involved in intestinal fluid secretion. Although these therapies have their own pros and cons inside the host, the quest for new antisecretory agents has been a successful elucidation to reduce burden of diarrheal disease.

Trends in prevalence of soil-transmitted helminth and major intestinal protozoan infections among school-aged children in Nepal.

OBJECTIVES: To assess the trends in prevalence of soil-transmitted helminths (STHs), Entamoeba histolytica and Giardia lamblia among school-aged children in Nepal between 1990 and 2015. METHODS: Systematic literature search in PubMed, MEDLINE, EMBASE, Google Scholar and local peer-reviewed journals for papers published between 1990 and December 2015. We conducted metaregression and meta-analyses to pool studies where applicable. RESULTS: Thirty-nine studies that examined a total of 14 729 stool specimens were included in the meta-analyses. The metaregression of prevalence of hookworms, roundworm, and whipworm showed a significantly decreasing trend over time. In or after 2004, the pooled prevalence of hookworm infections was 1.53% (95% CI, 0.73-2.59), of roundworm 4.31% (95% CI, 2.52-6.53) and of whipworm 2.89% (95% CI, 1.33-4.97) vs. 16.54% (95% CI, 7.64-27.97) for hookworm, 25.20% (95% CI, 13.59-38.97) for roundworm and 11.54% (95% CI 4.25-21.76) for whipworm in 1993-2003. E. histolytica and G. lamblia had stable prevalence since early 1990s, with a pooled prevalences of 4.12% (95% CI, 2.73-5.77) and 9.40% (95% CI, 7.15-11.92), respectively. The prevalence of G. lamblia was significantly higher in urban areas. CONCLUSIONS: We observed a sharp decrease in prevalence of STHs among school-aged children in Nepal in the past decade with prevalences dropping below 5% for STHs with no variation in prevalence in rural and urban areas. However, the prevalence of E. histolytica and G. lamblia remained stable over time. These results suggest that school-based deworming programmes rolled out during the study period had an observable impact on prevalence of STHs.

Protozoan Parasites.

• Stool antigen detection for Cryptosporidium sp, Giardia lamblia and Entamoeba histolytica are now commercially available, have better sensitivity and specificity than the traditional stool microscopy, and are less dependent on personnel skill. Tests employing newer techniques with faster turnaround time are also available for diagnosing trichomoniasis.• Nitazoxanide, the only U.S. Food and Drug Administration-approved medication for therapy of cryptosporidiosis, is effective among immunocompetent patients. However, on the basis of strong evidence from multiple clinical trials, nitazoxanide is considered ineffective among immunocompromised patients. (14) • Giardiasis can be asymptomatic or have a chronic course leading to malabsorption and failure to thrive. It can be treated with metronidazole, tinidazole, or nitazoxanide. On the basis of growing observational studies, postinfectious and extraintestinal manifestations of giardiasis occur, but the mechanisms are unclear. Given the high prevalence of giardiasis, public health implications need to be defined. (16) • Eradicating E histolytica from the gastrointestinal tract requires only intraluminal agent therapy. Therapy for invasive illnesses requires use of imidazole followed by intraluminal agents to eliminate persistent intraluminal parasites. • Malaria is considered the most lethal parasitic infection, with Plasmodium falciparum as the predominant cause of mortality. P vivax and P ovale can be dormant in the liver, and primaquine is necessary to resolve infection by P vivax and P ovale. • Among immunocompetent patients, infection with Toxoplasma gondii may be asymptomatic, involve localized lymphadenopathy, or cause ocular infection. In immunocompromised patients, reactivation or severe infection is not uncommon. On the basis of limited observational studies (there are no well-controlled randomized trials), therapy is recommended for acute infection during pregnancy to prevent transmission to the fetus/infant or decrease infectious sequelae to the fetus. (2) • On the basis of growing research evidence as well as consensus, trichomoniasis is associated with many health-related concerns, including adverse pregnancy outcomes and increased risk of acquisition and transmission of human immunodeficiency virus. (3)(25) Similar to toxoplasmosis,many infections are asymptomatic, and the true public health impact of trichomoniasis is difficult to define. Further research is warranted.