Seth E. O’Neal

Influence of Helminth Infections on the Clinical Course of and Immune Response to Leishmania braziliensis Cutaneous Leishmaniasis

BACKGROUND Helminth infections influence the clinical outcome of and immune response to certain immune-mediated diseases. METHODS We conducted a cohort study of 120 patients to examine the role that intestinal helminth infection plays in the clinical course of and immune response to cutaneous leishmaniasis (CL) treated with pentavalent antimony. RESULTS Patients coinfected with Leishmania braziliensis and helminths took longer to heal (relative hazard for healing, 0.47 [95% confidence interval, 0.26-0.85]; P=.01) than patients with CL without helminths, with 70% of coinfected patients being cured at 90 days, compared with 92% of helminth-free patients. Coinfected patients had an immune response shifted toward the T helper 2 type, with increased total immunoglobulin E levels (P<.06) and a tendency toward increased interleukin-5 levels, compared with helminth-free patients with CL. CONCLUSIONS Helminths influence both the clinical outcome and the immune response of patients with CL. These results may have clinical implications for the care of patients with CL caused by Leishmania braziliensis, because screening for and treatment of helminths may improve responses to treatment and possibly reduce the risk of progression to mucosal disease.

Elimination of Taenia solium Transmission in Northern Peru

BACKGROUND Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).

Taenia solium Tapeworm Infection, Oregon, 2006-2009.

Neurocysticercosis (NCC) is a parasitic disease caused by central nervous system infection with Taenia solium larval cysts. It is the most common helminthic infection of the central nervous system and a leading cause of acquired epilepsy in Latin America, Southeast Asia, and central Africa (1,2). The disease also is increasingly of clinical and public health concern in the United States, primarily in immigrants and travelers from cysticercosis-endemic regions (3–5). Cysticercosis is acquired through fecal–oral transmission of tapeworm eggs shed in the feces of a human carrying intestinal tapeworms. Ingested eggs release oncospheres, which invade the intestinal mucosa and disseminate throughout the body to form larval cysts. NCC occurs when cysts develop in the central nervous system and is the primary source of illness and death (6). The tapeworm’s complete life cycle occurs in regions with poor sanitary infrastructure, where foraging pigs have access to human feces. Most NCC cases in the United States probably were acquired in cysticercosis-endemic areas by immigrants or travelers who entered the United States already infected with cysts (3). However, immigrants and travelers also can harbor intestinal tapeworms, and domestic transmission of NCC does occur (7,8). Few states require reporting of cysticercosis; thus, population-based epidemiologic data in the United States are limited. Even in jurisdictions that require reporting, the clinical nature of NCC diagnosis complicates surveillance efforts because no single laboratory test definitively establishes the diagnosis. Surveillance therefore relies on clinician or institutional reporting. In 1989, California became the first state to require reporting; 112 cysticercosis cases were reported during the first year, for a crude annual incidence of 1.5 cases per 100,000 Hispanics (9). A retrospective case-series from Oregon based on hospital discharge diagnoses during 1995–2000 estimated an annual incidence of 0.2 cases per 100,000 general population and 3.1 cases per 100,000 Hispanics (10). In 5 cases, no exposure to a cysticercosis-endemic area was documented, which suggests the possibility of local transmission. Oregon adopted administrative rules for T. solium reporting in 2002 after the coroner’s examination implicated hydrocephalus secondary to obstructing ventricular cysts in 2 unexplained deaths (10). However, no subsequent efforts were undertaken to stimulate passive reporting or to actively find unreported cases. As a result, only 7 NCC cases, all in Hispanics, were reported to public health officials during the first 5 years of reporting. Oregon has a rapidly growing Hispanic population, which currently represents 11% of the total population. Approximately half of all Oregon Hispanics report birth outside the United States (11). In the context of an increasing population at risk, the small number of passively reported cases suggests inadequate surveillance. Identification and treatment of tapeworm carriers in the United States could prevent additional NCC cases. However, intestinal tapeworm infection produces few symptoms, and the prevalence is typically <1%–2%, even in regions where cysticercosis is endemic (12). During the 1980s, Los Angeles (LA) County, California, adopted a program of screening for tapeworm carriers with some success. By screening household members of NCC case-patients using light microscopy on fecal samples, the county identified an intestinal tapeworm carrier in 7% of its overall investigations and in 22% of investigations involving domestically acquired NCC (13). Improved screening methods have been developed in the interim, including an ELISA for Taenia sp. coproantigens in feces and an enzyme-linked immunoelectrotransfer blot (EITB) for serum antibodies against T. solium tapeworm (14,15). Serologic methods are desirable because they are specific to T. solium intestinal infection and highly sensitive (99%) and avoid the collection and processing of potentially infectious feces (15). Our objective was to evaluate the utility of public health surveillance for T. solium infection in Oregon. We implemented population-based active surveillance to determine the incidence of cysticercosis. We also piloted screening specifically for additional T. solium infection among affected households by using a combination of symptom screening, laboratory analysis of fecal and serum specimens, and radiographic imaging.

High Prevalence of Asymptomatic Neurocysticercosis in an Endemic Rural Community in Peru.

Background Neurocysticercosis is a common helminthic infection of the central nervous system and an important cause of adult-onset epilepsy in endemic countries. However, few studies have examined associations between neurologic symptoms, serology and radiographic findings on a community-level. Methodology We conducted a population-based study of resident’s ≥2 years old in a highly endemic village in Peru (pop. 454). We applied a 14 -question neurologic screening tool and evaluated serum for antibodies against Taenia solium cysticercosis using enzyme-linked immunoelectrotransfer blot (LLGP-EITB). We invited all residents ≥18 years old to have non-contrast computerized tomography (CT) of the head. Principal findings Of the 385 residents who provided serum samples, 142 (36.9%) were seropositive. Of the 256 residents who underwent CT scan, 48 (18.8%) had brain calcifications consistent with NCC; 8/48 (17.0%) reported a history of headache and/or seizures. Exposure to T. solium is very common in this endemic community where 1 out of 5 residents had brain calcifications. However, the vast majority of people with calcifications were asymptomatic. Conclusion This study reports a high prevalence of NCC infection in an endemic community in Peru and confirms that a large proportion of apparently asymptomatic residents have brain calcifications that could provoke seizures in the future.

Neurocysticercosis Among Resettled Refugees From Burma

Taenia solium is the most common helminthic infection of the central nervous system and a leading cause of epilepsy in developing nations. Little is known about neurocysticercosis in refugees from Southeast Asia which is endemic for T solium. We present two cases in a single household of refugees from Burma.

GPS Tracking of Free-Ranging Pigs to Evaluate Ring Strategies for the Control of Cysticercosis/Taeniasis in Peru

Background Taenia solium, a parasitic cestode that affects humans and pigs, is the leading cause of preventable epilepsy in the developing world. T. solium eggs are released into the environment through the stool of humans infected with an adult intestinal tapeworm (a condition called taeniasis), and cause cysticercosis when ingested by pigs or other humans. A control strategy to intervene within high-risk foci in endemic communities has been proposed as an alternative to mass antihelminthic treatment. In this ring strategy, antihelminthic treatment is targeted to humans and pigs residing within a 100 meter radius of a pig heavily-infected with cysticercosis. Our aim was to describe the roaming ranges of pigs in this region, and to evaluate whether the 100 meter radius rings encompass areas where risk factors for T. solium transmission, such as open human defecation and dense pig activity, are concentrated. Methodology/Principal Findings In this study, we used Global Positioning System (GPS) devices to track pig roaming ranges in two rural villages of northern Peru. We selected 41 pigs from two villages to participate in a 48-hour tracking period. Additionally, we surveyed all households to record the locations of open human defecation areas. We found that pigs spent a median of 82.8% (IQR: 73.5, 94.4) of their time roaming within 100 meters of their homes. The size of home ranges varied significantly by pig age, and 93% of the total time spent interacting with open human defecation areas occurred within 100 meters of pig residences. Conclusions/Significance These results indicate that 100 meter radius rings around heavily-infected pigs adequately capture the average pig’s roaming area (i.e., home range) and represent an area where the great majority of exposure to human feces occurs.

Taeniasis among Refugees Living on Thailand-Myanmar Border, 2012.

We tested refugee camp residents on the Thailand–Myanmar border for Taenia solium infection. Taeniasis prevalence was consistent with that for other disease-endemic regions, but seropositivity indicating T. solium taeniasis was rare. Seropositivity indicating cysticercosis was 5.5% in humans, and 3.2% in pigs. Corralling pigs and providing latrines may control transmission of these tapeworms within this camp.

Assessing Ultrasonography as a Diagnostic Tool for Porcine Cysticercosis

Background Taenia solium inflicts substantial neurologic disease and economic losses on rural communities in many developing nations. “Ring-strategy” is a control intervention that targets treatment of humans and pigs among clusters of households (rings) that surround pigs heavily infected with cysticerci. These pigs are typically identified by examining the animal’s tongue for cysts. However, as prevalence decreases in intervened communities, more sensitive methods may be needed to identify these animals and to maintain control pressure. The purpose of this study was to evaluate ultrasonography as an alternative method to detect pigs heavily infected with T. solium cysts. Methodology/Principal Findings We purchased 152 pigs representing all seropositive animals villagers were willing to sell from eight communities (pop. 2085) in Piura, Peru, where T. solium is endemic. Tongue and ultrasound examinations of the fore and hind-limbs were performed in these animals, followed by necropsy with fine dissection as gold standard to determine cyst burden. We compared the sensitivity and specificity of ultrasonography with tongue examination for their ability to detect heavy infection (≥ 100 viable cysts) in pigs. Compared to tongue examination, ultrasonography was more sensitive (100% vs. 91%) but less specific (90% vs. 98%), although these differences were not statistically significant. The greater sensitivity of ultrasound resulted in detection of one additional heavily infected pig compared to tongue examination (11/11 vs. 10/11), but resulted in more false positives (14/141 vs. 3/141) due to poor specificity. Conclusions/Significance Ultrasonography was highly sensitive in detecting heavily infected pigs and may identify more rings for screening or treatment compared to tongue examination. However, the high false positive rate using ultrasound would result in substantial unnecessary treatment. If specificity can be improved with greater operator experience, ultrasonography may benefit ring interventions where control efforts have stalled due to inadequate sensitivity of tongue examination.

Spatial relationship between Taenia solium tapeworm carriers and necropsy cyst burden in pigs

Background Taenia solium, a parasite that affects humans and pigs, is the leading cause of preventable epilepsy in the developing world. Geographic hotspots of pigs testing positive for serologic markers of T. solium exposure have been observed surrounding the locations of human tapeworm carriers. This clustered pattern of seropositivity in endemic areas formed the basis for geographically targeted control interventions, which have been effective at reducing transmission. In this study, we further explore the spatial relationship between human tapeworm carriers and infected pigs using necroscopic examination as a quantitative gold-standard diagnostic to detect viable T. solium cyst infection in pigs. Methodology/Principal findings We performed necroscopic examinations on pigs from 7 villages in northern Peru to determine the number of viable T. solium cysts in each pig. Participating humans in the study villages were tested for T. solium tapeworm infection (i.e., taeniasis) with an ELISA coproantigen assay, and the distances from each pig to its nearest human tapeworm carrier were calculated. We assessed the relationship between proximity to a tapeworm carrier and the prevalence of light, moderate, and heavy cyst burden in pigs. The prevalence of pig infection was greatest within 50 meters of a tapeworm carrier and decreased monotonically as distance increased. Pigs living less than 50 meters from a human tapeworm carrier were 4.6 times more likely to be infected with at least one cyst than more distant pigs. Heavier cyst burdens, however, were not more strongly associated with proximity to tapeworm carriers than light cyst burdens. Conclusion/Significance Our study shows that human tapeworm carriers and pigs with viable T. solium cyst infection are geographically correlated in endemic areas. This finding supports control strategies that treat humans and pigs based on their proximity to other infected individuals. We did not, however, find sufficient evidence that heavier cyst burdens in pigs would serve as improved targets for geographically focused control interventions.

Apuntes y recomendaciones para el establecimiento de programas de control de la teniasis / cisticercosis por Taenia solium en el Perú

Neurocysticercosis is a nervous system infection caused by the larvae (cysticercus) of the pork tapeworm (Taenia solium). Neurocysticercosis is the primary cause of acquired epilepsy worldwide and, therefore, a global public health problem. On the other hand, T. solium taeniasis/cysticercosis is one of very few infectious diseases considered to be potentially eradicable. Recently, a large-scale elimination program in Tumbes, Peru, demonstrated the feasibility of interrupting transmission. Based on these advances, a series of initial guidelines are proposed aimed at setting out the foundations for regional and national taeniasis/cysticercosis control programs, with simple and feasible local interventions as a starting point.