Multilevel modelling of the incidence of visceral leishmaniasis in Teresina, Brazil.

Epidemics of visceral leishmaniasis (VL) in major Brazilian cities are new phenomena since 1980. As determinants of transmission in urban settings probably operate at different geographic scales, and information is not available for each scale, a multilevel approach was used to examine the effect of canine infection and environmental and socio-economic factors on the spatial variability of incidence rates of VL in the city of Teresina. Details on an outbreak of greater than 1200 cases of VL in Teresina during 1993-1996 were available at two hierarchical levels: census tracts (socio-economic characteristics, incidence rates of human VL) and districts, which encompass census tracts (prevalence of canine infection). Remotely sensed data obtained by satellite generated environmental information at both levels. Data from census tracts and districts were analysed simultaneously by multilevel modelling. Poor socio-economic conditions and increased vegetation were associated with a high incidence of human VL. Increasing prevalence of canine infection also predicted a high incidence of human VL, as did high prevalence of canine infection before and during the epidemic. Poor socio-economic conditions had an amplifying effect on the association between canine infection and the incidence of human VL. Focusing interventions on areas with characteristics identified by multilevel analysis could be a cost-effective strategy for controlling VL. Because risk factors for infectious diseases operate simultaneously at several levels and ecological data usually are available at different geographical scales, multilevel modelling is a valuable tool for epidemiological investigation of disease transmission.

Application of an improved method for the recombinant k 39 enzyme-linked immunosorbent assay to detect visceral leishmaniasis disease and infection in Bangladesh.

Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement=0.970) and more reliable compared to the original method (kappa=0.587, P<0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kala-azar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.

The burden of Leishmania chagasi infection during an urban outbreak of visceral leishmaniasis in Brazil.

First noted in the city of Teresina in 1981, the last decades have witnessed a remarkable increase in urban transmission of American visceral leishmaniasis (VL) in many Brazilian cities. Teresina, the site of this study, has faced two large outbreaks of VL. The first occurred from 1981-1985 when almost 1000 new cases were reported. The second started in the 1990s, and between 1993 and 1996 more than 1200 new cases were detected. This report describes the prevalence of infection with Leishmania chagasi in Teresina at the end of the second outbreak and gives estimates of the number of people who became infected during the epidemic. Between June 1995 and May 1996, 200 households were chosen at random from a list of addresses covering about 93% of Teresina's urban households. In each household, one person over the age of 1 year was screened for Leishmania antibodies and skin-tested. Nearly 50% of persons had a positive leishmanin reaction, but only 13.9% had detectable antibodies to L. chagasi. While prevalence estimates based on the leishmanin skin-test increased with age (P<0.001), those based on serological tests showed a lesser, and non significant, variation with age (P=0.31). Using a geometric growth equation, and assuming that the annual distribution of clinical cases may serve as an approximation to what would have been the distribution of infections by year, we estimated that over 320000 persons were infected during the epidemic. Little is known about the epidemiology of VL in urban areas, where social networks, population density, and relationships of housing with the natural environment are more varied and complex than in the rural scene. In those areas, control interventions have failed to eliminate transmission of the parasite and prevent new epidemics. Further epidemiological studies of VL in urban areas might be needed to inform control actions.

Acquired immunodeficiency syndrome-related blastomycosis in an unusual geographic location.

Blastomycosis is a fungal infection acquired via inhalation of Blastomyces dermatitidis. The majority of cases occur in central, southeastern, and mid-Atlantic areas of the United States. We report the case of a 42-year-old veteran infected with the human immunodeficiency virus who presented in E1 Paso, Texas, with a dry cough, fever, and recent weight loss. We review the clinical and epidemiologic features of blastomycosis. Diagnostic criteria and pharmacologic management are discussed. Active duty personnel are at high risk of exposure to B. dermatitidis. Military providers should maintain an index of suspicion for blastomycosis in endemic and nonendemic regions.

Gastrointestinal infections in the immunocompromised host.

Gastrointestinal disease is a significant cause of morbidity and mortality in the immunocompromised patient. This article focuses on the infectious gastrointestinal complications associated with the treatment of malignant disease and with solid organ transplantation but not HIV. Gastrointestinal defenses and the various mechanisms by which they are impaired are reviewed. The major pathogens and malignancies of this patient population and an approach to their diagnosis, treatment, and prevention are discussed.

Competence of the human host as a reservoir for Leishmania chagasi.

The failure of control programs for visceral leishmaniasis (VL) that depend on elimination of infected dogs suggests that other reservoir hosts may participate in the transmission cycle. To determine whether persons infected with Leishmania chagasi can infect the vector sand fly, laboratory-reared Lutzomyia longipalpis were allowed to feed on Brazilian subjects with active, cured, and asymptomatic VL and on asymptomatic residents of houses of persons with active VL. Of 3747 insects that had fed, 26 acquired infection from 11 of the 44 persons with active VL, but none acquired infection from the 137 asymptomatic persons. Among persons <4 years old with active VL, a history of diarrhea and higher peripheral blood neutrophil counts were independent predictors of infectivity. Further experiments using larger numbers of insects are necessary to evaluate the reservoir competence of persons with asymptomatic infections, who represent a large segment of the population of several Brazilian cities.

Gender distribution in asymptomatic and invasive amebiasis.

OBJECTIVE: The majority of individuals infected by the protozoan parasite Entamoeba histolytica experience subclinical infections. However, a small proportion of parasitized individuals develop severe invasive disease such as amebic dysentery or amebic liver abscess. Invasive amebiasis affects predominantly men; the usual explanation for this has been that men have a higher rate of asymptomatic infections and therefore experience a higher rate of invasive disease. To date, there is no convincing evidence of an increased rate of asymptomatic infection of men as compared with women. The purpose of this study was to evaluate the evidence supporting the hypothesis that men have higher rates of asymptomatic infection and thus an increased frequency of invasive amebiasis. METHODS: We reviewed published reports of invasive amebiasis and population-based parasitological studies from 1929-1997 to compare the gender ratio of asymptomatic and symptomatic E. histolytica infection. Infections with E. histolytica were differentiated from the nonpathogenic E. dispar whenever possible. RESULTS: The reports of invasive amebiasis (dysentery, liver abscess, colonic perforation, peritonitis, appendicitis, and ameboma) showed a higher proportion of men than women (ratio, male:female = 3.2:1, p < 0.05). This contrasts with the epidemiological surveys, where the rate of asymptomatic infection with E. histolytica was the same (1:1) for both genders (p > 0.05). CONCLUSIONS: Asymptomatic E. histolytica infection is equally distributed between the genders. The high proportion of men with invasive amebiasis may be due to a male-related susceptibility to invasive disease.

Large epidemics of hemorrhagic fevers in Mexico 1545-1815.

In 1545, twenty-four years after the Spanish conquest of the Aztec empire, an epidemic of a malignant form of a hemorrhagic fever appeared in the highlands of Mexico. The illness was characterized by high fever, headache, and bleeding from the nose, ears, and mouth, accompanied by jaundice, severe abdominal and thoracic pain as well as acute neurological manifestations. The disease was highly lethal and lasted three to four days. It attacked primarily the native population, leaving the Spaniards almost unaffected. The hemorrhagic fevers remained in the area for three centuries and the etiologic agent is still unknown. In this report we describe, and now that more information is available, analyze four epidemics that occurred in Mexico during the colonial period with a focus on the epidemic of 1576 which killed 45% of the entire population of Mexico. It is important to retrieve such diseases and the epidemics they caused from their purely historical context and consider the reality that if they were to reemerge, they are potentially dangerous.

The American Society of Tropical Medicine and Hygiene initiative to stimulate educational programs to enhance medical expertise in tropical diseases.

More than a decade ago, at a time when current and emerging tropical diseases posed growing threats to the United States, expert panels convened by the Institute of Medicine of the U.S. National Academy of Sciences concluded that medical expertise within the United States competent to address diseases of the tropics had declined. Recognizing a national need to encourage and enhance such, The American Society of Tropical Medicine and Hygiene developed a program to stimulate new postgraduate medical education in diseases of the tropics. The Society formally requested academic institutions within the United States and Canada to propose new postgraduate programs. To assure the quality of these new curricular offerings, the Society developed an outline of key areas of competency and agreed to offer an examination that would grant physicians a Certificate of Knowledge in Clinical Tropical Medicine and Travelers Health. The certifying examination was to be an integral component of a program to stimulate academic institutions to provide instructional programs in tropical diseases and to encourage physicians to become trained, evaluated, and recognized for their knowledge of clinical tropical diseases and travelers' health. The Society's initiative to stimulate educational programs in tropical medicine is reviewed.

African trypanosomiasis in two travelers from the United States.

African trypanosomiasis is a rare but well-documented cause of fever in United States travelers returning from areas where it is endemic. We report two recently diagnosed cases that involved tourists who went on safari in Tanzania. Review of these and 29 other published cases indicates that disease in returning United States travelers is nearly always of the East African form, a fulminant illness for which prompt diagnosis is necessary. In the United States, timely and appropriate therapy for this disease has resulted in favorable outcomes for most patients. Chemoprophylaxis for East African trypanosomiasis is not recommended, but travelers visiting areas of endemicity should practice appropriate preventive measures to prevent tsetse fly bites.

Genetic characterization of an epidemic of Plasmodium falciparum malaria among Yanomami Amerindians.

Malaria parasites are genetically diverse at all levels of endemicity. In contrast, the merozoite surface protein (MSP) alleles in samples from 2 isolated populations of Yanomami Amerindians during an epidemic of Plasmodium falciparum were identical. The nonvariable restriction fragment length polymorphism patterns further suggested that the sequential outbreak comprised only a single P. falciparum genotype. By examination of serial samples from single human infections, the MSP characteristics were found to remain constant throughout the course of infection. An apparent clonal population structure of parasites seemed to cause outbreaks in small isolated villages. The use of standard molecular epidemiologic methods to measure genetic diversity in malaria revealed the occurrence of a genetically monomorphic population of P. falciparum within a human community.

Differential perpetuation of malaria species among Amazonian Yanomami Amerindians.

To determine whether malaria perpetuates within isolated Amerindian villages in the Venezuelan Amazon, we surveyed malaria infection and disease among 1,311 Yanomami in three communities during a 16-month period. Plasmodium vivax was generally present in each of these small, isolated villages; asymptomatic infection was frequent, and clinical disease was most evident among children less than five years of age (odds ratio [OR] = 6.3, 95% confidence interval [CI] = 1.4-29.2) and among persons experiencing parasitemias > or = 1,000 parasites/mm3 of blood (OR = 45.0, 95% CI = 5.5-370.7). Plasmodium falciparum, in contrast, was less prevalent, except during an abrupt outbreak in which 72 infections resulted in symptoms in all age groups and at all levels of parasitemia, and occasionally were life-threatening. The observed endemic pattern of P. vivax infection may derive from the capacity of this pathogen to relapse, while the epidemic pattern of P. falciparum infection may reflect occasional introductions of strains carried by immigrants or residents of distant villages and the subsequent disappearance of this non-relapsing pathogen.

Treatment of chronic, nonhealing abdominal wound in a liquid environment.

A 66-year-old woman with an abdominal wound caused by infected synthetic mesh had failed to heal in spite of many surgical attempts to close the wound. A sealed transparent vinyl chamber was glued to the periphery of the wound and antibiotics in high concentrations (up to 2,500 times the minimum inhibitory concentration) were delivered through the chamber. The wound fluid in the chamber was used for analysis of microbial activity, concentration of residual antibiotics, and growth factor activity. After 10 weeks of treatment, the wound was closed and has not recurred in 24 months.

Bubonic leishmaniasis: a common manifestation of Leishmania (Viannia) braziliensis infection in Ceara, Brazil.

Enlarged regional lymph nodes have been reported to accompany the cutaneous lesions of Leishmania (Viannia) braziliensis (= L. braziliensis). A survey in Ceara State, Brazil indicated that 77% of persons (456 of 595) with parasitologically confirmed cutaneous leishmaniasis reported lymphadenopathy in addition to skin lesions. A group of 169 persons with recently diagnosed leishmaniasis and lymph nodes measuring > or = 2 cm in diameter (mean = 3.6 cm, maximum = 10.5 cm) underwent detailed clinical examination. Lymphadenopathy preceded the skin lesions in more than two-thirds of these, on the average by two weeks. Cultures of lymph node aspirates yielded Leishmania more frequently (86%) than cultures of aspirates of skin (53%) or biopsies of skin (74%). Parasites were isolated from the peripheral blood of one patient. Persons with lymphadenopathy gave a history of fever and had enlarged livers or spleens more often than a comparison group of 50 persons with cutaneous lesions but no lymphadenopathy. Persons with lymphadenopathy had more intense leishmanin skin reactions and lymphocyte proliferation following stimulation with specific antigens, whereas persons without lymphadenopathy had a higher frequency of previous infection. Isolates of parasites from both groups were identified as L. braziliensis. These data demonstrate the early spread of L. braziliensis beyond the skin and suggest differences in host immunity between persons with and without lymphadenopathy. Leishmaniasis braziliensis should be considered in cases of unexplained lymphadenopathy in endemic areas.

Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. The New England Regional Toxoplasma Working Group.

BACKGROUND: Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. METHODS: In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. RESULTS: Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three). CONCLUSIONS: Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.

Schistosomiasis.

Schistosomiasis is a curable parasitic infection that, if left untreated, can persist for 30 years even though the parasite cannot reproduce in its human host. Tissue pathology, particularly of the GI and GU tracts, is associated with the granulomatous immune response to parasite eggs. Schistosomiasis is not endemic to the United States because the specific snail intermediate hosts required for transmission are absent. Physicians in North America will see acute and chronic forms of schistosomiasis in travelers and former residents of endemic areas. Therapy with praziquantel is indicated for all species of schistosomes and all clinical manifestations of schistosomiasis.

Diagnosis of Mycobacterium avium bacteremia by polymerase chain reaction.

We describe a rapid polymerase chain reaction (PCR)-based test for diagnosing Mycobacterium avium directly from blood specimens. Blood was collected in anticoagulant (EDTA) from patients who also had blood cultures performed by the lysis-centrifugation method. Blood samples were centrifuged on a Ficoll-Hypaque gradient to purify peripheral blood mononuclear cells. The purified cells were washed and incubated in the presence of Chelex-100 (a divalent cation-binding resin), boiled to release mycobacterial DNA, and then amplified with M. avium-specific PCR primers. Amplification was detected by hybridization with radiolabelled probe, and the results were compared with the culture results. The PCR assay gave positive results for 12 of 15 specimens that were taken from patients with positive cultures for M. avium complex (sensitivity, 80%). The three PCR-negative specimens in this group showed evidence of PCR inhibition. The PCR assay gave positive results for 32 of 228 specimens taken from patients with negative cultures (specificity, 86%). Of these 32 PCR-positive culture-negative specimens, 27 were also positive when amplified with primers specific for the genus Mycobacterium, suggesting that PCR may be more sensitive than culture.