Accuracy of Serological Testing for the Diagnosis of Prevalent Neurocysticercosis in Outpatients with Epilepsy,Eastern Cape Province,South Africa

Background

Few studies have estimated prevalence of neurocysticercosis (NCC) among persons with epilepsy in sub-Saharan Africa. While the limitations of serological testing in identification of NCC are well known, the characteristics of persons who are misdiagnosed based on serology have not been explored. The first objective of this pilot study was to estimate the prevalence of NCC in epilepsy outpatients from an area of South Africa endemic for cysticercosis. The second objective was to estimate the accuracy of serological testing in detecting NCC in these outpatients and characterize sources of disagreement between serology and neuroimaging.

Methodology/Principal Findings

All out-patients aged 5 or older attending the epilepsy clinic of St. Elizabeth''s Hospital in Lusikisiki, Eastern Cape Province, between July 2004 and April 2005 were invited to participate. Epidemiological data were collected by local study staff using a standardized questionnaire. Blood samples were tested by ELISA for antibody and antigen for Taenia solium. Four randomly chosen, consenting participants were transported each week to Mthatha for brain CT scan. The proportion of persons with epilepsy attending St. Elizabeth clinic with CT-confirmed NCC was 37% (95% CI: 27%–48%). Using CT as the gold standard, the sensitivity and specificity of antibody testing for identifying NCC were 54.5% (36.4%–71.9%) and 69.2% (52.4%–83.0%), respectively. Sensitivity improved to 78.6% (49.2%–95.3%) for those with active lesions. Sensitivity and specificity of antigen testing were considerably poorer. Compared to false negatives, true positives more often had active lesions. False positives were more likely to keep pigs and to have seizure onset within the past year than were true negatives.

Conclusions/Significance

The prevalence of NCC in South African outpatients with epilepsy is similar to that observed in other countries where cysticercosis is prevalent. Errors in classification of NCC using serology alone may reflect the natural history of NCC.     

Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on Seizures

Background

Neurocysticercosis accounts for 30%–50% of all late-onset epilepsy in endemic countries. We assessed the clustering patterns of Taenia solium human cysticercosis seropositivity and seizures around tapeworm carriers in seven rural communities in Peru.

Methodology

The presence of T. solium–specific antibodies was defined as one or more positive bands in the enzyme-linked immunoelectrotransfer blot (EITB). Neurocysticercosis-related seizures cases were diagnosed clinically and had positive neuroimaging or EITB.

Principal Findings

Eleven tapeworm carriers were identified by stool microscopy. The seroprevalence of human cysticercosis was 24% (196/803). Seroprevalence was 21% >50 m from a carrier and increased to 32% at 1–50 m (p = 0.047), and from that distance seroprevalence had another significant increase to 64% at the homes of carriers (p = 0.004). Seizure prevalence was 3.0% (25/837) but there were no differences between any pair of distance ranges (p = 0.629, Wald test 2 degrees of freedom).

Conclusion/Significance

We observed a significant human cysticercosis seroprevalence gradient surrounding current tapeworm carriers, although cysticercosis-related seizures did not cluster around carriers. Due to differences in the timing of the two outcomes, seroprevalence may reflect recent T. solium exposure more accurately than seizure frequency.     

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.     

Neurocysticercosis as a Cause of Epilepsy and Seizures in Two Community-Based Studies in a Cysticercosis-Endemic Region in Peru

Background

The prevalence of epilepsy added to inadequate treatment results in chronic morbidity and considerable mortality in poor populations. Neurocysticercosis (NCC), a helminthic disease of the central nervous system, is a leading cause of seizures and epilepsy in most of the world.

Methods

Taking advantage of a cysticercosis elimination program, we performed two community-based cross-sectional studies between 2006 and 2007 in 58 rural communities (population 20,610) to assess the prevalence and characteristics of epilepsy and epileptic seizures in this endemic region. Serological and computed tomography (CT) data in individuals with epilepsy were compared to previous surveys in general population from the same region.

Principal findings

In two surveys, 17,450 individuals were evaluated. Lifetime prevalence of epilepsy was 17.25/1000, and prevalence of active epilepsy was 10.8/1000 inhabitants. The prevalence of epilepsy increased after age 25 years and dropped after age 45. Only 24% (45/188) of patients with active epilepsy were taking antiepileptic drugs, all at sub-therapeutic doses. Antibodies to cysticercosis were found in approximately 40% of individuals with epilepsy in both studies. In one survey only individuals presenting strong antibody reactions were significantly associated with having epilepsy (OR 5.74; p<0.001). In the second, the seroprevalence as well as the proportion presenting strong antibody reactions were both significantly higher in individuals with epilepsy (OR 2.2 and 4.33, respectively). Brain CT showed NCC-compatible images in 109/282 individuals with epilepsy (39%). All individuals with viable parasites on CT were seropositive.

Conclusion

The prevalence of epilepsy in this cysticercosis endemic region is high and NCC is an important contributor to it.     

Rapid Identification of Paragonimiasis Foci by Lay Informants in Lao People's Democratic Republic

Background

Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases.

Methodology/Principal Findings

The study was carried out in an endemic area of Lao People''s Democratic Republic. Leaders of 49 remote villages in northern Vientiane Province were asked to notify suspected paragonimiasis patients using a four-item questionnaire sent through administrative channels: persons responding positively for having chronic cough (more than 3 weeks) and/or blood in sputum with or without fever. We validated the village leaders'' reports in ten representative villages with a door-to-door survey. We examined three sputa of suspected patients for the presence of Paragonimus eggs and acid fast bacilli. 91.8% of village leaders participated and notified a total of 220 suspected patients; 76.2% were eventually confirmed; an additional 138 suspected cases were found in the survey. Sensitivity of village leaders'' notice for “chronic cough” and “blood in sputum” was 100%; “blood in sputum” alone reached a sensitivity of 85.7%.

Significance

Our approach led to the identification of three previously unknown foci of transmission. A rapid and simple lay-informant questionnaire approach is a promising low-cost community diagnostic tool of paragonimiasis control programs.     

Seroprevalence to the Antigens of Taenia solium Cysticercosis among Residents of Three Villages in Burkina Faso: A Cross-Sectional Study

Background

There is limited published information on the prevalence of human cysticercosis in West Africa. The aim of this pilot study was to estimate the prevalence of Taenia solium cysticercosis antigens in residents of three villages in Burkina Faso.

Methods/Principal Findings

Three villages were selected: The village of Batondo, selected to represent villages where pigs are allowed to roam freely; the village of Pabré, selected to represent villages where pigs are usually confined; and the village of Nyonyogo, selected because of a high proportion of Muslims and limited pig farming. Clustered random sampling was used to select the participants. All participants were asked to answer an interview questionnaire on socio-demographic characteristics and to provide a blood sample. The sera were analysed using an AgELISA. The prevalence of “strong” seropositive results to the presence of antigens of the larval stages of T. solium was estimated as 10.3% (95%CI: 7.1%–14.3%), 1.4% (0.4%–3.5%) and 0.0% (0.0%–2.1%) in the 763 participants who provided a blood sample in Batondo, Pabré and Nyonyogo, respectively. The prevalence of “weak” seropositive test results to the presence of antigens of the larval stages of T. solium was 1.3% (0.3%–3.2%), 0.3% (0.0%–1.9%) and 4.5% (2.0%–8.8%) in Batondo, Pabré and Nyonyogo, respectively. The multivariate logistic regression, which included only Batondo and Pabré, showed that village, gender, and pork consumption history were associated with AgELISA seroprevalence.

Conclusions/Significance

This study illustrates two major points: 1) there can be large variation in the prevalence of human seropositivity to the presence of the larval stages of T. solium cysticercosis among rural areas of the same country, and 2) the serological level of the antigen, not just whether it is positive or negative, must be considered when assessing prevalence of human cysticercosis antigens.     

Prevalence of Livestock-Associated MRSA in Communities with High Pig-Densities in The Netherlands

Background

Recently, livestock-associated methicillin-resistant Staphylococcus aureus CC398 has been discovered in animals, livestock farmers and retail meat. This cross-sectional study aimed to determine the spread to persons not in direct contact with livestock in areas with a high density of pig farms.

Methodology/Principal Findings

With a random mailing in 3 selected municipalities in the Netherlands, adult persons were asked to fill in a questionnaire and to take a nose swab. In total, complete information was obtained on 583 persons. Of the 534 persons without livestock-contact, one was positive for MRSA (0.2%; 95% confidence interval, <0.01–1.2). Of the 49 persons who did indicate to be working at or living on a livestock farm, 13 were positive for MRSA (26.5%; 95% confidence interval, 16.1–40.4). All spa-types belonged to CC398.

Conclusions/Significance

Livestock-associated MRSA has a high prevalence in people with direct contact with animals. At this moment it has not spread from the farms into the community.     

A Cross-sectional Serological Study of Cysticercosis,Schistosomiasis, Toxocariasis and Echinococcosis in HIV-1 Infected People in Beira,Mozambique

Background

Helminthic infections are highly endemic in Mozambique, due to limited access to healthcare and resources for disease prevention. Data on the subclinical prevalence of these diseases are scarce due to the fact that an immunological and imaging diagnosis is not often available in endemic areas. We conducted a cross-sectional study on HIV1⁺ patients from Beira city in order to determine the seroprevalence of cysticercosis, schistosomiasis, toxocariasis and echinoccocosis and its possible interaction with HIV infection.

Methodology/Principal Findings

Patients (601) were voluntarily recruited at the Ponta Gea Health Center and their demographic and clinical data were recorded (including CD4⁺ cell count and antiretroviral regimen). Mean age was 39.7 years, 378 (62.9%) were women and 223 (37.1%) were men. Four hundred seventy-five (475) patients (79%) were already on highly active antiretroviral therapy (HAART), and 90 started therapy after being enrolled in the study. For serological testing we used a Multiplex Western Blot IgG from LDBIO Diagnostics. The overall seroprevalence was 10.2% for cysticercosis, 23% for schistosomiasis, 7.3% for toxocariasis and 17.3% for echinococcosis.

Conclusions/Significance

Neither age nor the CD4⁺ count were significantly associated with the seroprevalence of the helminths studied. However, patients with CD4⁺ between 200–500/µl had a higher seroprevalence to all helminths than those with less than 200/µl cells/and those with more than 500 cells/µl. Female gender was significantly associated with cysticercosis and schistosomiasis, and being in HAART with toxocariasis. Headache was significantly associated with cysticercosis and toxocariasis. There was no association between epilepsy and seropositivity to any of the parasites. The study concluded that a clear understanding of the prevalence and manifestations of these coinfections, how best to diagnose subclinical cases, and how to manage diseases with concomitant antiretroviral therapy is needed.     

T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease

Background

PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization.

Methodology

We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile.

Principal Findings

The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively.

Conclusions

The T. cruzi OligoC-TesT showed high sensitivity and specificity on a diverse panel of biological samples. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease.     

Trachoma Rapid Assessments in Unity and Northern Bahr-el-Ghazal States,Southern Sudan

Background

Trachoma is thought to be endemic over large parts of Southern Sudan, but empirical evidence is limited. While some areas east of the Nile have been identified as highly endemic, few trachoma surveys have been conducted in the remainder of the country. This study aimed to determine whether trachoma constitutes a problem to public health in Northern Bahr-el-Ghazal and Unity State, both located west of the Nile.

Methods and Principal Findings

Trachoma rapid assessments (TRA) were conducted between July and September 2009. Seven villages in Northern Bahr-el-Ghazal State and 13 villages in Unity State were surveyed; an average of 50 children (age 1–9 years) and 44 women (age 15 years and above) were examined per village. Samples for analysis using the APTIMA Combo-2 nucleic acid amplification test (NAAT) were collected from participants with active trachoma in eight villages in Unity State. In Northern Bahr-el-Ghazal State, only three children with active trachoma (trachomatous inflammation follicular (TF) and/or trachomatous inflammation intense (TI)) and two women with trichiasis (TT) were found, in two of the seven villages surveyed. In Unity State, trachoma was endemic in all thirteen villages surveyed; the proportion of children with active trachoma ranged from 33% to 75% between villages, while TF in children ranged from 16% to 44%. Between 4% to 51% of examined women showed signs of TT. Samples from active trachoma cases tested using the NAAT were positive for Chlamydia trachomatis infection for 46.6% of children and 19.0% of women.

Conclusions

Trachoma presents a major problem to public health Unity State, while the disease is of low priority in Northern-Bahr-el-Ghazal State. Implementation of a population-based prevalence survey is now required in Unity State to generate baseline prevalence data so that trachoma interventions can be initiated and monitored over time.     

High Burden of Impetigo and Scabies in a Tropical Country

Background

Impetigo and scabies are endemic diseases in many tropical countries; however the epidemiology of these diseases is poorly understood in many areas, particularly in the Pacific.

Methodology/Principal Findings

We conducted three epidemiological studies in 2006 and 2007 to determine the burden of disease due to impetigo and scabies in children in Fiji using simple and easily reproducible methodology. Two studies were performed in primary school children (one study was a cross-sectional study and the other a prospective cohort study over ten months) and one study was performed in infants (cross-sectional). The prevalence of active impetigo was 25.6% (95% CI 24.1–27.1) in primary school children and 12.2% (95% CI 9.3–15.6) in infants. The prevalence of scabies was 18.5% (95% CI 17.2–19.8) in primary school children and 14.0% (95% CI 10.8–17.2) in infants. The incidence density of active impetigo, group A streptococcal (GAS) impetigo, Staphylococcus aureus impetigo and scabies was 122, 80, 64 and 51 cases per 100 child-years respectively. Impetigo was strongly associated with scabies infestation (odds ratio, OR, 2.4, 95% CI 1.6–3.7) and was more common in Indigenous Fijian children when compared with children of other ethnicities (OR 3.6, 95% CI 2.7–4.7). The majority of cases of active impetigo in the children in our study were caused by GAS. S. aureus was also a common cause (57.4% in school aged children and 69% in infants).

Conclusions/Significance

These data suggest that the impetigo and scabies disease burden in children in Fiji has been underestimated, and possibly other tropical developing countries in the Pacific. These diseases are more than benign nuisance diseases and consideration needs to be given to expanded public health initiatives to improve their control.     

Helminth Infection and Eosinophilia and the Risk of Plasmodium falciparum Malaria in 1- to 6-Year-Old Children in a Malaria Endemic Area

Background

Helminth infection is common in malaria endemic areas, and an interaction between the two would be of considerable public health importance. Animal models suggest that helminth infections may increase susceptibility to malaria, but epidemiological data has been limited and contradictory.

Methodology/Principal Findings

In a vaccine trial, we studied 387 one- to six-year-old children for the effect of helminth infections on febrile Plasmodium falciparum malaria episodes. Gastrointestinal helminth infection and eosinophilia were prevalent (25% and 50% respectively), but did not influence susceptibility to malaria. Hazard ratios were 1 for gastrointestinal helminth infection (95% CI 0.6–1.6) and 0.85 and 0.85 for mild and marked eosinophilia, respectively (95% CI 0.56–1.76 and 0.69–1.96). Incident rate ratios for multiple episodes were 0.83 for gastro-intestinal helminth infection (95% CI 0.5–1.33) and 0.86 and 0.98 for mild and marked eosinophilia (95% CI 0.5–1.4 and 0.6–1.5).

Conclusions/Significance

There was no evidence that infection with gastrointestinal helminths or urinary schistosomiasis increased susceptibility to Plasmodium falciparum malaria in this study. Larger studies including populations with a greater prevalence of helminth infection should be undertaken.     

A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children

Background

The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC ⁻ ssaV ⁻) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile.

Objectives

We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years.

Methods

Subjects were randomly assigned to receive either a nominal dose of 5×10⁹ CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA.

Principal Findings

One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18–5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12–36%) of 50 subjects in the placebo group (odds ratio (OR) [95%CI]  = 1.23 [0.550–2.747]; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC ⁻ ssaV ⁻) ZH9 was detected in 51 (51%; 95% CI, 41–61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92–99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7–29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88–100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested.

Conclusions

This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children.

Trial Registration

Controlled-trials.comISRCTN91111837     

The Impact of Repeated Rounds of Mass Drug Administration with Diethylcarbamazine Plus Albendazole on Bancroftian Filariasis in Papua New Guinea

Background

This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration (MDA) on bancroftian filariasis in Papua New Guinea, which has the largest filariasis problem in the Pacific region.

Methodology/Principal Findings

Residents of rural villages near Madang were studied prior to and one year after each of three rounds of MDA with diethylcarbamazine plus albendazole administered per World Health Organization (WHO) guidelines. The mean MDA compliance rate was 72.9%. Three rounds of MDA decreased microfilaremia rates (Mf, 1 ml night blood by filter) from 18.6% pre-MDA to 1.3% after the third MDA (a 94% decrease). Mf clearance rates in infected persons were 71%, 90.7%, and 98.1% after 1, 2, and 3 rounds of MDA. Rates of filarial antigenemia assessed by card test (a marker for adult worm infection) decreased from 47.5% to 17.1% (a 64% decrease) after 3 rounds of MDA. The filarial antibody rate (IgG₄ antibodies to Bm14, an indicator of filarial infection status and/or exposure to mosquito-borne infective larvae) decreased from 59.3% to 25.1% (a 54.6% decrease). Mf, antigen, and antibody rates decreased more rapidly in children <11 years of age (by 100%, 84.2%, and 76.8%, respectively) relative to older individuals, perhaps reflecting their lighter infections and shorter durations of exposure/infection prior to MDA. Incidence rates for microfilaremia, filarial antigenemia, and antifilarial antibodies also decreased significantly after MDA. Filarial DNA rates in Anopheles punctulatus mosquitoes that had recently taken a blood meal decreased from 15.1% to 1.0% (a 92.3% decrease).

Conclusions/Significance

MDA had dramatic effects on all filariasis parameters in the study area and also reduced incidence rates. Follow-up studies will be needed to determine whether residual infection rates in residents of these villages are sufficient to support sustained transmission by the An. punctulatus vector. Lymphatic filariasis elimination should be feasible in Papua New Guinea if MDA can be effectively delivered to endemic populations.     

Active Trachoma and Ocular Chlamydia trachomatis Infection in Two Gambian Regions: On Course for Elimination by 2020?

Background

Trachoma has been endemic in The Gambia for decades. National trachoma control activities have been in place since the mid-1980''s, but with no mass antibiotic treatment campaign. We aimed to assess the prevalence of active trachoma and of actual ocular Chlamydia trachomatis infection as measured by polymerase chain reaction (PCR) in the two Gambian regions that had had the highest prevalence of trachoma in the last national survey in 1996 prior to planned national mass antibiotic treatment distribution in 2006.

Methodology/Principal Findings

Two stage random sampling survey in 61 randomly selected Enumeration Areas (EAs) in North Bank Region (NBR) and Lower River Region (LRR). Fifty randomly selected children aged under 10 years were examined per EA for clinical signs of trachoma. In LRR, swabs were taken to test for ocular C. trachomatis infection. Unadjusted prevalences of active trachoma were calculated, as would be done in a trachoma control programme. The prevalence of trachomatous inflammation, follicular (TF) in the 2777 children aged 1–9 years was 12.3% (95% CI 8.8%–17.0%) in LRR and 10.0% (95% CI 7.7%–13.0%) in NBR, with significant variation within divisions (p<0.01), and a design effect of 3.474. Infection with C. trachomatis was found in only 0.3% (3/940) of children in LRR.

Conclusions/Significance

This study shows a large discrepancy between the prevalence of trachoma clinical signs and ocular C. trachomatis infection in two Gambian regions. Assessment of trachoma based on clinical signs alone may lead to unnecessary treatment, since the prevalence of active trachoma remains high but C. trachomatis infection has all but disappeared. Assuming that repeated infection is required for progression to blinding sequelae, blinding trachoma is on course for elimination by 2020 in The Gambia.     

Phase II Evaluation of Sensitivity and Specificity of PCR and NASBA Followed by Oligochromatography for Diagnosis of Human African Trypanosomiasis in Clinical Samples from D.R. Congo and Uganda

Background

The polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) have been recently modified by coupling to oligochromatography (OC) for easy and fast visualisation of products. In this study we evaluate the sensitivity and specificity of the PCR-OC and NASBA-OC for diagnosis of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense human African trypanosomiasis (HAT).

Methodology and Results

Both tests were evaluated in a case-control design on 143 HAT patients and 187 endemic controls from the Democratic Republic of Congo (DRC) and Uganda. The overall sensitivity of PCR-OC was 81.8% and the specificity was 96.8%. The PCR-OC showed a sensitivity and specificity of 82.4% and 99.2% on the specimens from DRC and 81.3% and 92.3% on those from Uganda. NASBA-OC yielded an overall sensitivity of 90.2%, and a specificity of 98.9%. The sensitivity and specificity of NASBA-OC on the specimens from DRC was 97.1% and 99.2%, respectively. On the specimens from Uganda we observed a sensitivity of 84.0% and a specificity of 98.5%.

Conclusions/Significance

The tests showed good sensitivity and specificity for the T. b. gambiense HAT in DRC but rather a low sensitivity for T. b. rhodesiense HAT in Uganda.     

Characterisation of Clostridium difficile Hospital Ward–Based Transmission Using Extensive Epidemiological Data and Molecular Typing

Background

Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea and is endemic in hospitals, hindering the identification of sources and routes of transmission based on shared time and space alone. This may compromise rational control despite costly prevention strategies. This study aimed to investigate ward-based transmission of C. difficile, by subdividing outbreaks into distinct lineages defined by multi-locus sequence typing (MLST).

Methods and Findings

All C. difficile toxin enzyme-immunoassay-positive and culture-positive samples over 2.5 y from a geographically defined population of ∼600,000 persons underwent MLST. Sequence types (STs) were combined with admission and ward movement data from an integrated comprehensive healthcare system incorporating three hospitals (1,700 beds) providing all acute care for the defined geographical population. Networks of cases and potential transmission events were constructed for each ST. Potential infection sources for each case and transmission timescales were defined by prior ward-based contact with other cases sharing the same ST. From 1 September 2007 to 31 March 2010, there were means of 102 tests and 9.4 CDIs per 10,000 overnight stays in inpatients, and 238 tests and 15.7 CDIs per month in outpatients/primary care. In total, 1,276 C. difficile isolates of 69 STs were studied. From MLST, no more than 25% of cases could be linked to a potential ward-based inpatient source, ranging from 37% in renal/transplant, 29% in haematology/oncology, and 28% in acute/elderly medicine to 6% in specialist surgery. Most of the putative transmissions identified occurred shortly (≤1 wk) after the onset of symptoms (141/218, 65%), with few >8 wk (21/218, 10%). Most incubation periods were ≤4 wk (132/218, 61%), with few >12 wk (28/218, 13%). Allowing for persistent ward contamination following ward discharge of a CDI case did not increase the proportion of linked cases after allowing for random meeting of matched controls.

Conclusions

In an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic enzyme-immunoassay-positive patients cannot account for most new CDI cases. Please see later in the article for the Editors'' Summary     

Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

Introduction

Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.

Methods

Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).

Results

78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7–6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7–9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0–2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8–5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).

Conclusions

HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda.     

Spatial Clustering of Porcine Cysticercosis in Mbulu District,Northern Tanzania

Background

Porcine cysticercosis is caused by a zoonotic tapeworm, Taenia solium, which causes serious disease syndromes in human. Effective control of the parasite requires knowledge on the burden and pattern of the infections in order to properly direct limited resources. The objective of this study was to establish the spatial distribution of porcine cysticercosis in Mbulu district, northern Tanzania, to guide control strategies.

Methodology/Principal Findings

This study is a secondary analysis of data collected during the baseline and follow-up periods of a randomized community trial aiming at reducing the incidence rate of porcine cysticercosis through an educational program. At baseline, 784 randomly selected pig-keeping households located in 42 villages in 14 wards were included. Lingual examination of indigenous pigs aged 2–12 (median 8) months, one randomly selected from each household, were conducted. Data from the control group of the randomized trial that included 21 of the 42 villages were used for the incidence study. A total of 295 pig-keeping households were provided with sentinel pigs (one each) and reassessed for cysticercosis incidence once or twice for 2–9 (median 4) months using lingual examination and antigen ELISA. Prevalence of porcine cysticercosis was computed in Epi Info 3.5. The prevalence and incidence of porcine cysticercosis were mapped at household level using ArcView 3.2. K functions were computed in R software to assess general clustering of porcine cysticercosis. Spatial scan statistics were computed in SatScan to identify local clusters of the infection. The overall prevalence of porcine cysticercosis was 7.3% (95% CI: 5.6, 9.4; n = 784). The K functions revealed a significant overall clustering of porcine cysticercosis incidence for all distances between 600 m and 5 km from a randomly chosen case household based on Ag-ELISA. Lingual examination revealed clustering from 650 m to 6 km and between 7.5 and 10 km. The prevalence study did not reveal any significant clustering by this method. Spatial scan statistics found one significant cluster of porcine cysticercosis prevalence (P = 0.0036; n = 370). In addition, the analysis found one large cluster of porcine cysticercosis incidence based on Ag-ELISA (P = 0.0010; n = 236) and two relatively small clusters of incidence based on lingual examination (P = 0.0012 and P = 0.0026; n = 241). These clusters had similar spatial location and included six wards, four of which were identified as high risk areas of porcine cysticercosis.

Conclusion/Significance

This study has identified local clusters of porcine cysticercosis in Mbulu district, northern Tanzania, where limited resources for control of T. solium could be directed. Further studies are needed to establish causes of clustering to institute appropriate interventions.     

Toxocariasis and epilepsy: systematic review and meta-analysis

Objective

Human toxocariasis is a zoonotic infection caused by the larval stages of Toxocara canis (T. canis) and less frequently Toxocara cati (T. cati). A relationship between toxocariasis and epilepsy has been hypothesized. We conducted a systematic review and a meta-analysis of available data to evaluate the strength of association between epilepsy and Toxocara spp. seropositivity and to propose some guidelines for future surveys.

Data Sources

Electronic databases, the database from the Institute of Neuroepidemiology and Tropical Neurology of the University of Limoges (http://www-ient.unilim.fr/) and the reference lists of all relevant papers and books were screened up to October 2011.

Methods

We performed a systematic review of literature on toxocariasis (the exposure) and epilepsy (the outcome). Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio (OR) was estimated using a random-effects meta-analysis model of aggregated published data.

Results

Seven case-control studies met the inclusion criteria, for a total of 1867 participants (850 cases and 1017 controls). The percentage of seropositivity (presence of anti-Toxocara spp. antibodies) was higher among people with epilepsy (PWE) in all the included studies even if the association between epilepsy and Toxocara spp. seropositivity was statistically significant in only 4 studies, with crude ORs ranging 2.04–2.85. Another study bordered statistical significance, while in 2 of the included studies no significant association was found. A significant (p<0.001) common OR of 1.92 [95% confidence interval (CI) 1.50–2.44] was estimated. Similar results were found when meta-analysis was restricted to the studies considering an exclusively juvenile population and to surveys using Western Blot as confirmatory or diagnostic serological assay.

Conclusion

Our results support the existence of a positive association between Toxocara spp. seropositivity and epilepsy. Further studies, possibly including incident cases, should be performed to better investigate the relationship between toxocariasis and epilepsy.