Toxoplasma gondii-specific IgG avidity testing in pregnant women.

BACKGROUND: The parasite Toxoplasma gondii can cause congenital toxoplasmosis following primary infection in a pregnant woman. It is therefore important to distinguish between recent and past infection when both T. gondii-specific IgM and IgG are detected in a single serum in pregnant women. Toxoplasma gondii-specific IgG avidity testing is an essential tool to help to date the infection. However, interpretation of its results can be complex. OBJECTIVES: To review the benefits and limitations of T. gondii-specific avidity testing in pregnant women, to help practitioners to interpret the results and adapt the patient management. SOURCES: PubMed search with the keywords avidity, toxoplasmosis and Toxoplasma gondii for articles published from 1989 to 2019. CONTENT: Toxoplasma gondii-specific IgG avidity testing remains a key tool for dating a T. gondii infection in immunocompetent pregnant women. Several commercial assays are available and display comparable performances. A high avidity result obtained on a first-trimester serum sample is indicative of a past infection, which occurred before pregnancy. To date, a low avidity result must still be considered as non-informative to date the infection, although some authors suggest that very low avidity results are highly suggestive of recent infections depending on the assay. Interpretation of low or grey zone avidity results on a first-trimester serum sample, as well as any avidity result on a second-trimester or third-trimester serum sample, is more complex and requires recourse to expert toxoplasmosis laboratories. IMPLICATIONS: Although used for about 30 years, T. gondii-specific avidity testing has scarcely evolved. The same difficulties in interpretation have persisted over the years. Some authors have proposed additional thresholds to exclude an infection of <9 months, or in contrast to confirm a recent infection. Such thresholds would be of great interest to adapt management of pregnant women and avoid unnecessary treatment; however, they need confirmation and further studies.

Hepatic Cystic Echinococcosis (Hydatid Cyst) in a Six Year Old.

Presentation To describe a case of cystic echinococcosis (CE) in a previously healthy child and review epidemiology of CE in Ireland. Diagnosis A previously healthy 6 year old girl was found to have a cystic lesion in the right lobe of her liver. Serology for Echinococcus granulosus was positive, and radiological features were suggestive of CE. Treatment The patient was pre-treated with anti-helminthic medications before undergoing a liver segmentectomy to remove the cyst, and received further treatment with albendazole after surgery. Histological findings were consistent with CE due to E. granulosus, likely acquired during travel to continental Europe. Conclusion CE should be considered in the differential of children with asymptomatic cysts in the liver and/or lung, and a travel history elucidated in such cases.

Samples From Cases of Delusional Parasitosis as Seen in the UK Parasitology Reference Laboratory (2014-2015).

Delusional parasitosis is a common syndrome seen in Infectious Diseases clinics. These patients characteristically provide samples as evidence of their infestation. We prospectively catalogued and characterized 138 samples from these patients, processed in the UK Clinical Parasitology reference laboratory from January 2014 to April 2015. No human parasites were identified.

Hepatic alveolar hydatid disease (Echinococcus multilocularis), a mimic of liver malignancy: a review for the radiologist in non-endemic areas.

Alveolar hydatid disease or alveolar echinococcosis (AE) is caused by the parasite Echinococcus multilocularis and is increasingly seen as an imported disease in non-endemic areas such as the UK. It is rare compared to cystic echinococcosis (CE), but like CE commonly affects the liver. AE does have imaging features that can aid in diagnosis, but is often initially misdiagnosed as liver malignancy. It is usually fatal if untreated, underscoring the importance of early diagnosis. This review highlights the role of imaging in AE diagnosis with the broader objective of increasing radiologists' awareness of this unusual, but increasingly prevalent disease.

Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions.

BACKGROUND: Giardia intestinalis is microaerophilic diarrhoea-causing protozoan common in countries with suboptimal sanitation. Standard treatment is with nitroimidazoles, but a growing number of refractory cases is being reported. Treatment failure has become increasingly prevalent in travellers who contract giardiasis in Asia. Clinicians are increasingly falling back on second-line and less well-known drugs to treat giardiasis. AIMS: To review nitroimidazole-refractory G. intestinalis infection, examine the current efficacy of standard therapeutic agents, consider potential resistance mechanisms which could cause treatment failure and describe the practical aspects of managing this emerging clinical problem. SOURCES: A PubMed search was conducted using combinations of the following terms: refractory, Giardia, giardiasis, resistance and treatment. Articles on the pharmacotherapy, drug resistance mechanisms and use of alternative agents in nitroimidazole-refractory giardiasis were reviewed. CONTENT: We review the standard drugs for giardiasis, including their efficacy in initial treatment, mode of action and documented in vitro and in vivo drug resistance. We assess the efficacy of alternative drugs in nitroimidazole-refractory disease. Existing data suggest a potential advantage of combination treatment. IMPLICATIONS: An optimal treatment strategy for refractory giardiasis has still to be determined, so there is no standard treatment regimen for nitroimidazole-refractory giardiasis. Further work on drug resistance mechanisms and the use of drug combinations in this condition is a priority.

Increased incidence of nitroimidazole-refractory giardiasis at the Hospital for Tropical Diseases, London: 2008-2013.

Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens.

Detection of malarial DNA in blood donors--evidence of persistent infection.

BACKGROUND AND OBJECTIVES: The English transfusion service has screened donations from malaria-risk donors for malarial antibodies for over 10 years. The donor population includes migrants from many malaria-endemic countries and, from our experiences with post-transfusion malaria, some of these may remain parasitaemic and need clinical review. MATERIALS AND METHODS: Malarial antibody screen-reactive donations with serological evidence of malaria identified by the reference laboratory were further investigated for the presence of malarial DNA. RESULTS: Malarial DNA was found in 14 of 1955 samples investigated; three P. falciparum, five P. vivax, three P. ovale, two P. malariae and one dual parasitaemia P. falciparum/P. malariae. All of these were donors whose malaria risk was residency rather than travel. CONCLUSION: Malarial parasitaemia in healthy donors occurs, and donor malaria-risk strategies must take into account the possibility of such donors presenting. Countries not utilizing malarial antibody screening should consider carefully the collection of donations from donors previously resident in endemic countries; temporary deferral is insufficient.

Migrant health and infectious diseases in the UK: findings from the last 10 years of surveillance.

BACKGROUND: Migrants account for an increasing proportion of the UK population. They are at risk of acquiring infectious diseases in their country of origin (prior to migration or during return visits), during migration, as well as in their destination country. Migrants can therefore have different risk profiles to the indigenous population. METHODS: UK enhanced surveillance data for TB, HIV, malaria and enteric fever were analysed, with a focus on 2010, for migrant (non-UK born) populations. RESULTS: South Asia was the most common region of birth for TB and enteric fever cases (57 and 80% of migrant cases, respectively). Sub-Saharan Africa was the predominant region of birth for HIV in heterosexuals and malaria cases (80 and 75% of migrant cases, respectively). The majority of cases of TB, HIV in heterosexuals, malaria and enteric fever reported in the UK are migrants. Among UK-born cases, ethnic minorities are disproportionately represented. CONCLUSIONS: This analysis highlights the importance of considering, and improving the recording of, country of birth as a risk factor for infection. Consideration of multiple health risks is of value for migrant patients, and this has implications for the design of improved preventative strategies.

Invasive aspergillosis associated with pulmonary hydatid disease.

A patient presented with a cavitating lung lesion. Serology and sputum microscopy led to the diagnosis of pulmonary hydatid disease. However, histology of the operative samples revealed aspergillosis in the cavity and surrounding lung tissue. This is the first report of invasive aspergillosis occurring as a consequence of spontaneous hydatid cyst rupture.

Recommendations for the practice of travel medicine.

Travel Medicine has emerged as a distinct entity over the last two decades in response to a very substantial increase in international travel and is now forging its own identity, remit and objectives for care of the traveller. Crucial to the formation of any speciality is the definition of recommendations for its practice. This is particularly important and needed for travel medicine as it overlaps with and forms part of day-to-day work in a number of different medical specialities. This document defines a set of recommendations for the practice of travel medicine from the Faculty of Travel Medicine of the Royal College of Physicians and Surgeons of Glasgow. Their objective is to help raise standards of practice and achieve greater uniformity in provision of services, better to protect those who travel. As travel medicine moves towards applying for speciality status, these standards will also contribute to that process.

Chagas disease in European countries: the challenge of a surveillance system.

A study of aggregate data collected from the literature and official sources was undertaken to estimate expected and observed prevalence of Trypanosoma cruzi infection, annual incidence of congenital transmission and rate of underdiagnosis of Chagas disease among Latin American migrants in the nine European countries with the highest prevalence of Chagas disease. Formal and informal data sources were used to estimate the population from endemic countries resident in Europe in 2009, diagnosed cases of Chagas disease and births from mothers originating from endemic countries. By 2009, 4,290 cases had been diagnosed in Europe, compared with an estimated 68,000 to 122,000 expected cases. The expected prevalence was very high in undocumented migrants (on average 45% of total expected cases) while the observed prevalence rate was 1.3 cases per 1,000 resident migrants from endemic countries. An estimated 20 to 183 babies with congenital Chagas disease are born annually in the study countries. The annual incidence rate of congenital transmission per 1,000 pregnancies in women from endemic countries was between none and three cases. The index of under diagnosis of T. cruzi infection was between 94% and 96%. Chagas disease is a public health challenge in the studied European countries. Urgent measures need to be taken to detect new cases of congenital transmission and take care of the existing cases with a focus on migrants without legal residency permit and potential difficulty accessing care.

Serological analysis of the outcome of treatment of Schistosoma mansoni infections with praziquantel.

A serological assay was developed to assess the outcome of the treatment of intestinal schistosomiasis with praziquantel, in patients with Schistosoma mansoni infection. Each of 33 patients (seven found to be excreting S. mansoni eggs and 26 egg-negatives found seropositive for antibodies against antigens from S. mansoni eggs) had two to five serum specimens assayed, the sera being collected at the time of diagnosis and at least once after praziquantel treatment. The sera were tested in ELISA against three antigen preparations: the unfractionated soluble egg antigens of S. margrebowiei and S. mansoni (SmSEA) and a cationic antigen fraction (CEF6) purified from the SmSEA. The dynamics of the post-treatment antibody levels were variable. In a minority of the patients, antibody levels declined relatively rapidly (within 5-12 months), to ELISA negativity, with the levels of the anti-CEF6 antibodies declining more rapidly than those of the anti-SmSEA antibodies. In the remaining patients, however, the levels of these specific antibodies declined only slowly or not at all over a 2- to 3-year period. The post-treatment monitoring of the levels of anti-schistosome-egg antibodies, particularly those of anti-CEF6 antibodies, may help to distinguish the treatments that result in parasitological cure from those that are only partially successful.

External quality assessment scheme for parasite serology; a review of the scheme design and performance.

BACKGROUND: An external quality assessment (EQA) scheme for parasite serology was introduced in April 2005 as a tool to measure how well laboratories were performing in parasite serodiagnosis. AIM AND METHODS: To review the scheme design and performance from its beginning until January 2008. RESULTS: The numbers of participating laboratories gradually increased during the review period and was 28 in January 2008. The results showed that the standard of reporting was extremely high and there was an encouraging trend towards improvement in the overall percentage of correct reports. The most common error made was the returning of false negative results for Strongyloides antibodies. CONCLUSION: It is hoped that this scheme will lead to a more standardised approach to the serological diagnosis of parasitic infection.

Development of a new assay for the diagnosis of schistosomiasis, using cercarial antigens.

We have developed a new ELISA for detection of anti-schistosome antibodies using an extract from Schistosoma mansoni cercariae. We evaluated the new assay on serum samples sent to the Hospital for Tropical Diseases, Department of Clinical Parasitology, London, UK, by comparing it with our routinely used S. mansoni soluble egg antigen (SEA) assay. We also evaluated the new assay for cross-reactivity with a number of helminth and other infections. We demonstrate that the cercarial antigen assay is equivalent to the SEA assay for serodiagnosis of schistosomiasis in a non-endemic setting. The cercarial antigen preparation is more easily produced than SEA, and for this reason this assay may be preferred for routine clinical use and may be amenable to scaling up. Further assessment is needed before it can be recommended for use in an endemic area, as chronic disease and co-infection with other helminths are likely to be under-represented in our sample set.

Estimating unreported malaria cases in England: a capture-recapture study.

A capture-recapture study was undertaken to estimate the incidence and likely total burden of malaria cases in England. Cases diagnosed by the national Malaria Reference Laboratory (MRL) between July 2003 and December 2004 were matched with cases reported to Hospital Episode Statistics using demographic, geographical, parasitological, and temporal information. A total of 3861 cases were recorded in one or both datasets; the 'unknown population' was estimated as 746 cases (95% CI 677-822) giving a total of 4607 cases (95% CI 4446-4767) over 18 months. Eighty-four percent (95% CI 83-85) of cases were recorded in one or both datasets. Fifty-six percent (95% CI 54-58) of cases were captured by the MRL surveillance system; ascertainment for Plasmodium falciparum and London cases was higher at 66% and 62%, respectively. Improving case ascertainment will facilitate effective measures to reduce the burden of this preventable disease in the UK.

An eye-catching acanthocephalan.

Acanthocephala are endoparasitic worms with a characteristic retractile proboscis bearing rows of thorny hooks. They have been found in all classes of vertebrates; however, human infection appears to be rare and accidental. To date, all reported cases of acanthocephalans in humans have involved the gastrointestinal tract. Here we report for the first time the highly unusual finding of an immature acanthocephalan retrieved from a patient's eye.

Microscopic diagnosis of sodium acetate-acetic acid-formalin-fixed stool samples for helminths and intestinal protozoa: a comparison among European reference laboratories.

The present study aimed to compare the diagnostic performance of different European reference laboratories in diagnosing helminths and intestinal protozoa, using an ether-concentration method applied to sodium acetate-acetic acid-formalin (SAF)-preserved faecal samples. In total, 102 stool specimens were analysed during a cross-sectional parasitological survey in urban farming communities in Côte d'Ivoire. Five SAF-preserved faecal samples were prepared from each specimen and forwarded to the participating reference laboratories, processed and examined under a microscope adhering to a standard operating procedure (SOP). Schistosoma mansoni (cumulative prevalence: 51.0%) and hookworm (cumulative prevalence: 39.2%) were the predominant helminths. There was excellent agreement (kappa > 0.8; p < 0.001) among the reference laboratories for the diagnosis of S. mansoni, hookworm, Trichuris trichiura and Ascaris lumbricoides. Moderate agreement (kappa = 0.54) was found for Hymenolepis nana, and lesser agreement was observed for other, less prevalent helminths. The predominant intestinal protozoa were Entamoeba coli (median prevalence: 67.6%), Blastocystis hominis (median prevalence: 55.9%) and Entamoeba histolytica/Entamoeba dispar (median prevalence: 47.1%). Substantial agreement among reference laboratories was found for E. coli (kappa = 0.69), but only fair or moderate agreement was found for other Entamoeba species, Giardia intestinalis and Chilomastix mesnili. There was only poor agreement for B. hominis, Isospora belli and Trichomonas intestinalis. In conclusion, although common helminths were reliably diagnosed by European reference laboratories, there was only moderate agreement between centres for pathogenic intestinal protozoa. Continued external quality assessment and the establishment of a formal network of reference laboratories is necessary to further enhance both accuracy and uniformity in parasite diagnosis.

Praziquantel: neglected drug? Ineffective treatment? Or therapeutic choice in cystic hydatid disease?

The role of praziquantel in hydatid disease has not been well defined. This review evaluates the evidence on the use of praziquantel in treatment of cystic hydatid disease from in vitro and in vivo animal studies, human clinical studies and case reports. Praziquantel may prevent the vesicular evolution of protoscoleces and inhibit the formation of secondary cysts. It may also contribute to the loss of viability of small cysts before cyst differentiation and development of the fibrous adventitial layer. There is some evidence to support a role for the use of praziquantel in combination with albendazole in pre- and post-intervention chemotherapy for hydatid disease. Combined therapy may reduce the risk of disease recurrence and intraperitoneal seeding of infection that develops via cyst rupture and spillage occurring spontaneously or during surgery or percutaneous procedures. At present, there is insufficient published evidence to support a clear recommendation for the use of praziquantel in prolonged chemotherapy for established hydatid disease for which surgery is not indicated or in severe disseminated disease and further work is necessary. Randomised controlled studies to determine the efficacy and optimum duration of praziquantel treatment in combination with albendazole are required so that treatment recommendations for its use can finally be clarified.

The role of a recombinant hybrid protein based ELISA for the serodiagnosis of Onchocerca volvulus.

AIMS: Onchocerca volvulus infection is traditionally diagnosed by examination of skin snips for the presence of microfilariae. A disadvantage of this method is the low sensitivity particularly with light or prepatent infection. Serodiagnosis using recombinant-antigen-based assays may provide a more sensitive diagnostic test. An ELISA based on a recombinant antigen OvH3 has previously been validated using sera from endemic areas. This study investigated the role of this ELISA-based assay for use in the serodiagnosis of onchocerciasis in non-endemic areas. METHODS: The ELISA-based assay was tested on sera from untreated patients with known onchocerciasis and on untreated and treated patients with definite or probable onchocerciasis identified from a hospital diagnostic database. The assay was also tested on sera from patients with other helminthic infections to determine the sensitivity and specificity of this assay in a tertiary referral laboratory dealing with sera from a variety of patients. RESULTS: The sensitivity and specificity of the OvH3 assay were 93.2% and 93.5%, respectively, when tested on non-endemic patients with clinical diagnosis of onchocerciasis. CONCLUSIONS: This study demonstrates the potential role of the assay as a sensitive and specific test for use in the serodiagnosis of onchocerciasis in a reference laboratory dealing with sera from patients in non-endemic setting.