Rodney Hoff

Neonatal Serologic Screening and Early Treatment for Congenital Toxoplasma gondii Infection

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.

Epidemiological aspects of three Trypanosoma cruzi zymodemes in Bahia State, Brazil

Culture forms of 104 stocks of Trypanosoma cruzi isolated in different regions of the State of Bahia were compared by electrophoresis of six enzymes. The three distinct combinations of isoenzyme patterns seen were designated ZI, Z2 and Z3. In an area of endemic Chagass disease in eastern Bahia, T. cruzi Z1 was associated with sylvatic mammals and sylvatic triatomines, whereas T. cruzi Z2 was associated with a separate domestic cycleof transmission. T. cruzi Z1 was also found in sylvatic triatomines from other parts of the State. In contrast, in an area of the São Francisco Valley region of western Bahia, both T. cruzi Z1 and Z2 were isolated from man, domestic animals, and peridomestic rats. T. cruzi Z3 was isolated from an armadillo and from Panstrongylus geniculatus, a triatomine commonly found in armadillo burrows. Both T. cruzi Z1 and Z2 appeared to be pathogenic in man: T. cruzi Z1 was isolated from patients with acute Chagass disease and from a single patient with chronic cardiac manifestations. T. cruzi Z2 was isolated from some asymptomatic individuals but was also associated with acute disease and chronic cardiac and digestive syndromes.

An outbreak of acute Chagas's disease in the São Francisco Valley region of Bahia, Brazil: triatomine vectors and animal reservoirs of Trypanosoma cruzi

Following reports of an unusually high incidence of acute Chagass disease and the appearance of large numbers of Triatoma infestans in the southwestern region of the State of Bahia, triatomine bugs (Hemiptera: Reduviidae) and domestic animals in one of the affected communities were surveyed and examined for infection with Trypanosoma cruzi. Triatoma infestans was prevalent in houses and was also found in peridomestic habitats. T. sordida and T. pseudomaculata occupied peridomestic and sylvatic habitats and T. brasiliensis was found only among rocks far from houses. Panstrongylus megistus, formerly present in the region, was not found. Trypanosoma cruzi was detected in 19.5% of Triatoma infestans, 11.5% of T. sordida, 19% of dogs, 29% of cats and 100% of rats examined. A disproportionate number of early instar bugs were infected with Trypanosoma cruzi, suggesting that a rapid increase in the rate of transmission had recently occurred. The history of the domestic triatomine fauna of the region since 1912 is reviewed, and it is proposed that the relatively recent arrival of Triatoma infestans initiated a domestic cycle linked to peridomestic and sylvatic cycles of Trypanosoma cruzi transmission. Increased human mobility, the use of DDT for malaria control, and drought conditions are considered as factors which might have contributed to the outbreak of human infection.

Heterogeneous distribution of neuraminidase activity in strains and clones of Trypanosoma cruzi and its possible association with parasite myotropism

Various strains, stocks, and clones of Trypanosoma cruzi were analyzed for neuraminidase (NA) activity using fetuin and human erythrocytes as substrate. In all cases the activity was found to be developmentally regulated. Zymodeme type I strains, which are histotropic for skeletal muscle, had greater NA activity than zymodeme type II strains which are histotropic for either macrophages or cardiac muscle cells. Heterogeneity of NA expression within strains is suggested by the finding that one Silvio X10 clone had greater NA activity than another clone of the same stock. The differences observed were more pronounced when human erythrocytes and not fetuin were used as substrate. Trypomastigotes of the high producing strains reared in bovine artery smooth muscle cells had enhanced expression compared to trypomastigotes reared in 3T3 or human fibroblast cells. The first harvest of trypomastigotes from cell cultures had greater NA activity than trypomastigotes harvested on subsequent days.

Comparison of filtration staining (Bell) and thick smear (Kato) for the detection and quantitation of Schistosoma mansoni eggs in faeces

We compare results of one Bell and one Kato-Katz examination performed on each of 315 stool specimens from residents in an area in north-eastern Brazil endemic for schistosomiasis mansoni. The prevalence of Schistosome infection detected by the Bell technique was 76% and by the Kato-Katz technique was 63%. 81% (44/54) of the infections missed by a Kato-Katz smear were light infections (one of 50 epg range by Bell examination). Over, all, 55% (44/80) of stools in this egg count range by the Bell technique were negative on a single Kato-Katz smear. This implies that five Kato-Katz smears per stool would ensure a 95% probability (0.55(5) X 100) of detecting such light infections. However, a single Kato-Katz smear detected eggs in 97% (124/128) of stools with a Bell count greater than 100 epg. For stools positive by both methods the egg counts per gram of stool were higher (p less than 0.001) by Kato-Katz examination. Geometric mean egg counts for the infected population were 199 epg by the Kato-Katz and 92 epg by the Bell methods. 64% (59 v. 36) more persons were classified as heavily infected (greater than 400 epg) by the Kato-Katz method than by the Bell method. The differing measurements of schistosome infection obtained with the Bell and Kato-Katz methods must be considered when comparing data on morbidity-infection relationships.

Manson's schistosomiasis in Brazil: 11-year evaluation of successful disease control with oxamniquine.

This prospective study has shown that oxamniquine treatment controlled endemic schistosomiasis mansoni in a defined rural population in Castro Alves, north-east Brazil. Data before and after treatment spanning 11 years were collected for a cohort of 191 residents. Before treatment (1974-77), the cohort was heavily infected and the prevalence of associated hepatomegaly (greater than 86%) and splenomegaly (greater than 17%) was stable. The cohort was treated when oxamniquine became available in 1977; during the next 8 years, over 80% received further treatments from the Brazilian programme for the control of schistosomiasis. With treatment, the incidence of splenomegaly fell (10% to 2%) and the splenomegaly regression rate increased (43% to 91%). Declining disease rates were coincident with substantial falls in the prevalence and intensity of Schistosoma mansoni infections. The final prevalence rates for hepatomegaly (31%) and splenomegaly (3%) in Castro Alves approached the corresponding rates of 10% and 1% in a comparable uninfected control population.

A three year follow-up of chemotherapy with oxamniquine in a Brazilian community with endemic schistosomiasis mansoni

Oral oxamniquine was tested as a control strategy for endemic schistosomiasis in a rural area of Bahia, Brazil. Adults were treated with a single dose (12.5 to 15 mg per kg) and children (less than 12 years old) with a total of 20 mg per kg in two doses. The 191 (infected) persons treated represented 69% of the infected population in the study area. Follow-up stool examinations (Kato-Katz method) at one, 3, 6, 13, 25 and 33 months showed the cure rate declining from 80% at three months to 46% at 33 months. Over one half of those not cured showed a decrease in egg counts throughout the follow-up which, after 33 months, remained 66% below the pre-treatment levels. Stool examinations conducted on all study area residents during three years before chemotherapy showed the prevalence and intensity of Schistosoma mansoni infection to be high and stable. 33 months after the chemotherapy the prevalence was 41% and for infected individuals the geometric mean egg count was 121 epg, a decline of respectively 35% and 40% from pre-treatment levels for each index. Chemotherapy of infected persons with oxamniquine protected the community as a whole from high worm burdens for almost three years, although at this point the prevalence began to rise towards pretreatment levels.

THREE-YEAR PROSPECTIVE STUDY OF THE EVOLUTION OF MANSON'S SCHISTOSOMIASIS IN NORTH-EAST BRAZIL

A cross-sectional study of morbidity associated with Schistosoma mansoni infection in an area in North-East Brazil where the disease is endemic was carried out in 1974. The survey was repeated in 1977, before mass treatment with oxamniquine, providing a cohort of 210 individuals who had both examinations. The high prevalence of hepatomegaly (over 80%) and of splenomegaly (over 15%) contrasted with rates of 10% and 1%, respectively, in a non-endemic area. Over the 3-year period hepatomegaly spontaneously regressed in 13% of patients, and splenomegaly regressed in 56%, a phenomenon most common in older individuals with light infections. Those with heavy infections--ie, 500 or more eggs per g faeces, had an excess risk of splenomegaly of 19.6% and, of its persistence, of 61.5%. Thus, intensity of infection was a critical factor in liver and spleen involvement, and programmes of chemotherapy that reduce infection should mitigate the risk of schistosomal morbidity.

Congenital Chagas’s disease in an urban population: investigation of infected twins

In the Nordeste de Amaralina suburb of Salvador Bahia, Brazil, 47 of 285 pregnant women surveyed had complement fixing antibodies to Trypanosoma cruzi. At delivery T. cruzi was detected in one of 17 placentas from the sero-positive women. The offspring of this case were premature twins and T. cruzi was detected in the peripheral blood of each before death. At autopsy the gastro-intestinal tract and urinary bladder of both were severely affected. Immunofluorescence tests on cord sera, including the single case with T. cruzi in the placenta, were negative for IgM antibodies to T. cruzi. The mother of the infected twins and three of her living children, who were born and have resided in the city, were also infected with T. cruzi. Although the children had visited an area endemic for Chagass disease for short periods, the mode of transmission in this family may have been transplacental. The value of the immunofluorescence test in the diagnosis of congenital Chagass disease is discussed.

Cutaneous allergic reactions to Triatoma infestans after xenodiagnosis

We determined the frequency of cutaneous allergic reactions to bites of Triatoma infestans during xenodiagnosis in a rural community where Panstrongylus megistrus is the only domestic vector of Trypanosoma cruzi. Localized urticaria or more intense cutaneous allergic reactions at 48 and 72 hours were observed in 86.7% and 82.1% respectively of the individuals in our study. Urticaria was more severe in children and older adults and in women than in men. The high frequency of reactions suggests either cutaneous reactivity to T. infestans without prior sensitization or cross reactivity between P. megistus and T. infestans. A single application of topical corticosteroid or antihistamine medication did not reduce the cutaneous reactions.