Katja Polman

Strongyloidiasis - the most neglected of the neglected tropical diseases?

Soil-transmitted helminths of the genus Strongyloides (S. fuelleborni and the more prevalent S. stercoralis) are currently believed to infect an estimated 30-100 million people worldwide. The health consequences of S. stercoralis infections range from asymptomatic light infections to chronic symptomatic strongyloidiasis. Uncontrolled multiplication of the parasite (hyperinfection) and potentially life-threatening dissemination of larvae to all internal organs is found among individuals with compromised immune system functions. This paper provides an overview of the current state of the art in relation to diagnostic methods for detecting the infection, the morbidity caused by the infection and the recommended treatment. It further discusses some of the reasons why this infection is so neglected and the consequence of this for the estimated global prevalence. The paper finally points to the gaps in our knowledge and future research needs related to this infection. As Strongyloides infections have the potential to develop into severe disease in certain population subgroups, untreated infections could cause serious problems in the community. Therefore, we need to carefully investigate this parasite in order to develop and implement effective control programmes.

Molecular diagnosis of Strongyloides stercoralis in faecal samples using real-time PCR

A real-time PCR method targeting the small subunit of the rRNA gene was developed for the detection of Strongyloides stercoralis DNA in faecal samples, including an internal control to detect inhibition of the amplification process. The assay was performed on a range of well-defined control samples (n=145), known positive faecal samples (n=38) and faecal samples from a region in northern Ghana where S. stercoralis infections are highly endemic (n=212), and achieved 100% specificity and high sensitivity. The use of this assay could facilitate monitoring the prevalence and intensity of S. stercoralis infections during helminth intervention programs. Moreover, the use of this assay in diagnostic laboratories could make the introduction of molecular diagnostics feasible in the routine diagnosis of S. stercoralis infections, with a two-fold increase in the detection rate as compared with the commonly used Baermann sedimentation method.

Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence

This paper summarizes and concludes in‐depth field investigations on suspected resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70–90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitologically negative 12 weeks after treatment, although the reduction in mean egg counts was within normal ranges (86%). Among other hypotheses to explain the observed low cure rate in this focus, the possibility of drug resistance or tolerance had to be considered. Subsequent field trials with a shorter follow‐up period (6–8 weeks) yielded cure rates of 31–36%. Increasing the dose to 2 × 30 mg/kg did not significantly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resulted in a normal cure rate of 79%. The efficacy of praziquantel in this focus could be related to age and pre‐treatment intensity but not to other host factors, including immune profiles and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an urban region with no transmission, and re‐treatment after 3 weeks of non‐cured individuals within the area resulted in normal cure rates (78–88%). The application of an epidemiological model taking into account the relation between egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reduction after treatment with praziquantel; in average endemic situations, such a drug efficacy would result in normal cure rates. Laboratory studies by others on the presence or absence of praziquantel resistance in Senegalese schistosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel‐resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and intense transmission in this area.

Multiplex real-time PCR for the detection and quantification of Schistosoma mansoni and S. haematobium infection in stool samples collected in northern Senegal

A multiplex real-time PCR assay for the detection and quantification of Schistosoma mansoni and S. haematobium DNA in faecal samples was developed and evaluated as an alternative diagnostic method to study the epidemiology of schistosomiasis. Primers and probes targeting the cytochrome c oxidase gene were designed for species-specific amplification and were combined with an internal control. Using positive control DNA extracted from adult Schistosoma worms and negative control samples (n=150) with DNA from a wide range of intestinal microorganisms, the method proved to be sensitive and 100% specific. For further evaluation, duplicate stool specimens with varying S. mansoni egg loads were collected in northern Senegal from pre-selected individuals (n=88). The PCR cycle threshold values, reflecting parasite-specific DNA loads in faeces, showed significant correlation with microscopic egg counts both for S. mansoni in stool and S. haematobium in urine. The Schistosoma detection rate of PCR (84.1%) was similar to that of microscopy performed on duplicate stool samples (79.5%). The simple faecal sample collection procedure and the high throughput potential of the multiplex real-time PCR provide a powerful diagnostic tool for epidemiological studies on schistosomiasis in remote areas, with possibilities for extension to other helminths or protozoa using additional molecular targets.

Bidirectional Introgressive Hybridization between a Cattle and Human Schistosome Species

Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions, caused by parasitic flatworms of the genus Schistosoma (subclass Digenea). Following major water development schemes in the 1980s, schistosomiasis has become an important parasitic disease of children living in the Senegal River Basin (SRB). During molecular parasitological surveys, nuclear and mitochondrial markers revealed unexpected natural interactions between a bovine and human Schistosoma species: S. bovis and S. haematobium, respectively. Hybrid schistosomes recovered from the urine and faeces of children and the intermediate snail hosts of both parental species, Bulinus truncatus and B. globosus, presented a nuclear ITS rRNA sequence identical to S. haematobium, while the partial mitochondrial cox1 sequence was identified as S. bovis. Molecular data suggest that the hybrids are not 1st generation and are a result of parental and/or hybrid backcrosses, indicating a stable hybrid zone. Larval stages with the reverse genetic profile were also found and are suggested to be F1 progeny. The data provide indisputable evidence for the occurrence of bidirectional introgressive hybridization between a bovine and a human Schistosoma species. Hybrid species have been found infecting B. truncatus, a snail species that is now very abundant throughout the SRB. The recent increase in urinary schistosomiasis in the villages along the SRB could therefore be a direct effect of the increased transmission through B. truncatus. Hybridization between schistosomes under laboratory conditions has been shown to result in heterosis (higher fecundity, faster maturation time, wider intermediate host spectrum), having important implications on disease prevalence, pathology and treatment. If this new hybrid exhibits the same hybrid vigour, it could develop into an emerging pathogen, necessitating further control strategies in zones where both parental species overlap.

Helminths and malignancy.

It has been estimated that chronic infections with viruses, bacteria and parasites contribute to 17·8% of the global burden of cancer, although only a relatively small proportion of the infection‐related cancers can be attributed to helminth infections. These are important because of the high number of people who are exposed or infected worldwide. Carcinogenesis associated with helminth infections is a complex process, which may involve several different mechanisms, but chronic inflammation is a key feature. Host immune responses and immunopathological processes mediate inflammatory responses and any failure in the control of the immunological components involved in this response can lead to chronic inflammation. This may generate a microenvironment that might be conducive to the initiation and development of cancer. Inflammatory cells generate free radicals and nitrogen species, which can oxidize and damage DNA and lead to genetic instabilities and malignant transformation. Physical damage caused by the parasites, their eggs or secreted products leads to restorative hyperplasia of the damaged tissue. This may promote the propagation of cells, in which genotoxic damage and pre‐malignant change has taken place. Three helminth infections have been classified as definitely carcinogenic to humans (group 1 carcinogens), namely Schistosoma haematobium, which is associated with cancer of the urinary bladder and the food‐borne liver flukes Clonorchis sinensis and Opisthorchis viverrini associated with cholangiocarcinoma of the liver. Reducing the level of infection and the risk of getting (re)infected will reduce the risk of cancer development later in life. Helminth infections are thus a preventable cause of cancer, emphasizing the need for sustainable helminth control in endemic areas coupled with health education, especially in relation to food‐borne liver fluke infections.

Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests

BackgroundPersistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests.MethodsWe searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail.ResultsOver 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification.ConclusionsDiagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.

Association of atopy, asthma, allergic rhinoconjunctivitis, atopic dermatitis and intestinal helminth infections in Cuban children

Objective  To examine the relationship of past and current intestinal helminth infections with asthma, allergic rhinoconjunctivitis, atopic dermatitis and atopy.

Prevalence and risk factors of intestinal parasites in Cuban children.

Objectives  To determine the prevalence of intestinal parasite infections and their risk factors in children in urban and rural settings in two Cuban municipalities.

Taenia solium cysticercosis in the Democratic Republic of Congo : how does pork trade affect the transmission of the parasite?

Background Taenia solium, a zoonotic parasite that is endemic in most developing countries where pork is consumed, is recognised as the main cause of acquired epilepsy in these regions. T. solium has been reported in almost all of the neighboring countries of Democratic Republic of Congo (DRC) but data on the current prevalence of the disease in the country itself are lacking. This study, focusing on porcine cysticercosis (CC), makes part of a first initiative to assess whether cysticercosis is indeed actually present in DRC. Methods An epidemiological study on porcine CC was conducted (1) on urban markets of Kinshasa where pork is sold and (2) in villages in Bas-Congo province where pigs are traditionally reared. Tongue inspection and ELISA for the detection of circulating antigen of the larval stage of T. solium were used to assess the prevalence of active CC in both study sites. Findings The overall prevalence of pigs with active cysticercosis did not significantly differ between the market and the village study sites (38.8 [CI95%: 34–43] versus 41.2% [CI95%: 33–49], respectively). However, tongue cysticercosis was only found in the village study site together with a significantly higher intensity of infection (detected by ELISA). Interpretation Pigs reared at village level are sold for consumption on Kinshasa markets, but it seems that highly infected animals are excluded at a certain level in the pig trade chain. Indeed, preliminary informal surveys on common practices conducted in parallel revealed that pig farmers and/or buyers select the low infected animals and exclude those who are positive by tongue inspection at village level. This study provides the only recent evidence of CC presence in DRC and gives the first estimates to fill an important gap on the African taeniasis/cysticercosis distribution map.