Miguel M. Cabada

Treatment of cryptosporidiosis: do we know what we think we know?

Purpose of review The management of cryptosporidiosis is fraught with controversies. New research on diagnostics and medications has reached the field in recent years. Therefore, familiarity with key features of current management tools is important. We discuss diagnostic and therapeutic aspects of cryptosporidiosis focusing on evidence behind the medications available to date. Recent findings Molecular methods provide a clearer understanding of cryptosporidiosis epidemiology. The major determinants of severity still are host immune status and parasite species. Children and immunosuppressed individuals, especially with HIV/AIDS, are disproportionately affected. Nitazoxanide is an important advance in treatment of HIV negative patients. However, recent research confirms the limited effectiveness of antiparasitic drugs to treat cryptosporidiosis in AIDS. Questions remain about using partially active drugs paromomycin and nitazoxanide for treatment. Potent antiretroviral combinations modify disease epidemiology and are key components of therapy in AIDS. However, it is unclear whether this is due solely to immune reconstitution or due in part to antiparasitic effects of HIV protease inhibitors. Newer candidate drugs are in development. Summary There is better understanding of the epidemiology of cryptosporidiosis and promising new diagnostic methods. There are significant challenges in terms of control and treatment of cryptosporidiosis among the groups at risk.

Sexual behavior of international travelers visiting Peru

Background Sexual behavior of travelers to Latin America and the sexual behavior of US travelers in general are poorly characterized. Goal The goal of the study was to evaluate sexual risk factors of travelers to Peru. Study Design Anonymous written questionnaires were administered to 442/507 (87%) of the individuals approached in the international departures area of the Lima airport. Results Of the 442 respondents, 54 (12.2%) had new sex partners during their stay. Sex with a local partner (35/52; 67.3%) was more frequent than sex with other travelers (18/52; 34.6%) or with sex workers (4/52; 7.7%). Risk factors for a new sex partner included male sex (relative risk, 1.94), single marital status (relative risk, 2.59), duration of stay longer than 30 days (relative risk, 5.05), traveling alone or with friends (relative risk, 2.88), and bisexual orientation (relative risk, 4.94). Frequency of sexual activity among US travelers was greater than that among travelers from other countries (15.2% [22/145] versus 10.6% [30/282]; NS). Condoms were consistently used by 12/50 (24%) and sometimes used by 10/50 (20%), including 8/20 United States travelers and 13/29 travelers from other countries. Conclusion Behaviors and risk factors are similar to those described for travelers to Africa, Asia, and Eastern Europe. Behavior of US travelers did not differ from that of other travelers.

Sexual behavior in travelers visiting Cuzco.

BACKGROUND In South America, little is known about sexual behavior and risk factors for acquiring sexually transmitted diseases (STDs) among travelers and among local people sexually interacting with travelers. There is evidence that, in Peru, significant sexual interaction between these groups exists. METHOD An anonymous written questionnaire was administered to travelers in the airport and bus stations before they left Cuzco. RESULTS Of the travelers,5.6% engaged in sexual activity with a new partner during their stay in Cuzco. Sexual intercourse with other travelers was most common (76/140, 54.3%), followed by sex with local partners (57/140, 40.7%), and with commercial sex workers (3/140, 2.15%). Consistent condom use was reported by 97/140 (69.3%). In the multivariate analysis, the following variables were independently associated with casual sex: male gender, single marital status, age between 15 and 35 years, non-United States travelers (NUSTs), traveling alone or with friends, length of stay more than 30 days, homosexual or bisexual orientation, and expectation of having sex before traveling. Homosexual and bisexual travelers had 3 or more new sexual partners more frequently than heterosexual travelers (4/8, 18/129, OR=6.17 (1.16<OR<33.5)). NUSTs received more pretravel advice (698/1587, 210/718, OR=1.86 (1.54<OR<2.24)) and engaged in more sexual activity (100/1,587, 25/722, OR=1.86 (1.20<OR<2.93)) than United States travelers (USTs). CONCLUSION Travelers visiting Cuzco engage in sexual activities that put them at risk of acquiring STD and transmitting it, both in their home country and in Peru. We recommend the inclusion of Peru and possibly other Latin American countries in the list of destinations where there is substantial risk of transmission of STD and the provision of pretravel advice regarding this issue to travelers to Peru.

Human primary intestinal epithelial cells as an improved in vitro model for Cryptosporidium parvum infection.

ABSTRACT The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens.

Recombinase polymerase amplification-based assay to diagnose Giardia in stool samples.

Giardia duodenalis is one of the most commonly identified parasites in stool samples. Although relatively easy to treat, giardiasis can be difficult to detect as it presents similar to other diarrheal diseases. Here, we present a recombinase polymerase amplification-based Giardia (RPAG) assay to detect the presence of Giardia in stool samples. The RPAG assay was characterized on the bench top using stool samples spiked with Giardia cysts where it showed a limit-of-detection nearly as low as the gold standard polymerase chain reaction assay. The RPAG assay was then tested in the highlands of Peru on 104 stool samples collected from the surrounding communities where it showed 73% sensitivity and 95% specificity against a polymerase chain reaction and microscopy composite gold standard. Further improvements in clinical sensitivity will be needed for the RPAG assay to have clinical relevance.

Pretravel Health Advice among International Travelers Visiting Cuzco, Peru

BACKGROUND Cuzco, a Peruvian city of historical interest located 3,326 m above sea level, is a frequent destination for tourists. We conducted a descriptive study to assess the extent and sources of pretravel health advice received by international travelers before their arrival to Cuzco. METHODS Data were collected as part of a health survey among travelers. Between August and November 2002, travelers between 15 and 65 years old were invited to fill out a questionnaire in the departing area of Cuzcos international airport. RESULTS A total of 5,988 travelers participated. The mean age was 35.4 years (SD 11.4 yr); 50.6% were female and 50.8% were single. Tourism was the reason for traveling in 90.2% of the participants, and 89.3% of them were traveling with companions. Pretravel health information was received by 93.6%. The median number of information sources was two, with books (41.5%), travel medicine clinics (38.8%), the Internet (23.3%), and general practitioners (22.7%) as the main sources. Most frequently received recommendations were about safe food and water consumption (85%), use of insect repellents (66.0%), sunburn protection (64.4%), and condom use (22%). Only 16.5% took medication to prevent altitude sickness, and 14.2% took medication to prevent travelers diarrhea. Variables independently associated with receiving pretravel health information from a health care professional were female gender, country of residence other than the United States, length of stay in Cuzco > 7 days, length of stay in other Peruvian cities > 7 days, tourism as the main reason for visiting Cuzco, traveling with companions, and consulting of more than one source of information. CONCLUSIONS Most travelers arriving to Cuzco had received pretravel health information, and the majority obtained it from more than one source. Recommendations addressed for specific health risks, such as altitude sickness prophylaxis, were received by few travelers.

Treatment of cryptosporidiosis

Cryptosporidiosis is caused by intracellular parasites of the genus Cryptosporidium, which has been recognized as a human pathogen since 1976. Two species are responsible for most human infections: Cryptosporidium hominis, which primarily infects humans, and Cryptosporidium parvum, which infects humans and animals such as cattle. In immunocompetent individuals, infection causes self-limited watery diarrhea that lasts approximately 5–10 days. However, in immunocompromised individuals, especially HIV/AIDS patients, cryptosporidiosis may present as chronic diarrhea or severe, cholera-like illness, leading to wasting, malabsorption of antiretroviral drugs and reduced life expectancy. Cryptosporidiosis also affects malnourished children in developing countries, with negative long-term effects on growth, weight gain, and physical and cognitive development [1]. Even asymptomatic infections are associated with growth deficits [2] and infants with cryptosporidiosis may have an increased risk of all-cause mortality persisting into the second year of life [3]. However, Cryptosporidium also has important public health implications for developed countries. Cryptosporidium spp. are known to cause traveller’s diarrhea [4] and to be responsible for outbreaks of diarrhea that are often associated with recreational water, such as waterparks, or the municipal water supply [5].

Frequent HTLV-1 infection in the offspring of Peruvian women with HTLV-1-associated myelopathy/tropical spastic paraparesis or strongyloidiasis

OBJECTIVES To describe the frequency of HTLV-1 infection among offspring of mothers who had presented with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), strongyloidiasis, or asymptomatic HTLV-1 infection, and to identify factors associated with HTLV-1 infection. METHODS In a descriptive study, records were reviewed of HTLV-1-positive women and their offspring who had been tested for HTLV infection at a public hospital in Lima, Peru, from 1989 to 2003. Sons and daughters of women who had presented with strongyloidiasis, HAM/TSP, or asymptomatic infection were eligible for this study. RESULTS Three hundred seventy subjects were included: 279 were the offspring of 104 mothers presenting with HAM/TSP, 58 were the offspring of 22 mothers with strongyloidiasis, and 33 were the offspring of 26 asymptomatic mothers. Mean age of the offspring at the time of testing was 26 years (standard deviation 12). Nineteen percent of the offspring tested positive for HTLV-1: 6% (2/33) of those with asymptomatic mothers, 19% (52/279) among the offspring of mothers with HAM/TSP, and 31% (18/58) among the offspring of mothers presenting with strongyloidiasis On multiple logistic regression analysis, three factors were significantly associated with HTLV-1: (a) duration of breast-feeding (odds ratio [OR] = 15.1; [4.2-54.1] for 12 to 24 months versus less than 6 months breast-feeding); (b) clinical condition of the mother (OR = 8.3 [1.0-65.3] for HAM/TSP and OR = 11.5 [1.4-98.4] for strongyloidiasis in comparison with offspring of asymptomatic mothers); and (c) transfusion history (OR = 5.5 [2.0-15.2]). CONCLUSIONS In addition to known risk factors for HTLV-1 transmission (duration of breast-feeding and history of blood transfusion), maternal HAM/TSP and strongyloidiasis were associated with seropositivity among offspring of HTLV-1-infected mothers.

New developments in epidemiology, diagnosis, and treatment of fascioliasis.

Purpose of review This review focuses on the recent developments in the epidemiology, burden of disease, diagnostic tests, and treatment of fascioliasis. Recent findings Recent epidemiologic data suggest that either the endemic areas are expanding or disease is being recognized in areas where it was not previously observed. In addition, recent data highlight the effects of fascioliasis on childhood anemia and nutrition. Diagnosis remains problematic, but newer diagnostic tests including antibody, antigen, and DNA detection tests may facilitate earlier diagnosis. Recent studies suggest that point-of-care testing may soon be possible. Treatment with triclabendazole is effective, but resistance is emerging in livestock and may pose a threat for patients. Summary Fascioliasis continues to emerge as an important neglected disease, with new studies highlighting the under-recognized burden of disease. Further studies are needed on burden of disease, improved diagnosis, and alternative to triclabendazole treatment.

Acute Mountain Sickness Impact Among Travelers to Cusco, Peru

BACKGROUND Increasing numbers of travelers are visiting high altitude locations in the Andes. The epidemiology of acute mountain sickness (AMS) among tourists to high altitude in South America is not well understood. METHODS A cross-sectional study to evaluate the epidemiology, pre-travel preparation, and impact of AMS among travelers to Cusco, Peru (3,400 m) was performed at Cuscos International Airport during June 2010. Foreign travelers, 18 years or older, staying 15 days or less, departing Cusco were invited to participate. Demographic, itinerary, and behavioral data were collected. The Lake Louise Clinical score (LLCS) was used to assess AMS symptoms. RESULTS In total, 991 travelers participated, median age 32 years (interquartile range 25-49), 55.5% female, 86.7% tourists, mostly from the United States (48.2%) and England (8.1%). Most (76.7%) flew from sea level to Cusco and 30.5% visited high altitude in the previous 2 months. Only 29.1% received AMS advice from a physician, 19% recalled advice on acetazolamide. Coca leaf products (62.8%) were used more often than acetazolamide (16.6%) for prevention. AMS was reported by 48.5% and 17.1% had severe AMS. One in five travelers with AMS altered their travel plans. Travelers older than 60 years, with recent high altitude exposure, who visited lower cities in their itinerary, or used acetazolamide were less likely to have AMS. Using coca leaf products was associated with increased AMS frequency. CONCLUSIONS AMS was common and adversely impacted plans of one in five travelers. Acetazolamide was associated with decreased AMS but was prescribed infrequently. Other preventive measures were not associated with a decrease in AMS in this population. Pre-travel preparation was suboptimal.