Chagas disease as example of a reemerging parasite

Trypanosoma cruzi, the protozoan that causes Chagas disease, is primarily transmitted by three main Triatomine vectors in endemic areas. However, the infection has become a potential emerging disease because the vector is found in non-endemic areas, there is migration of infected asymptomatic people that can infect the vector, become blood donors, or pass the disease vertically (congenital infections). Lastly, the disease can be acquired through contaminated food (oral transmission). This review will present the different transmission pathways, clinical manifestations, diagnostic modalities and treatment considerations of Chagas disease.     

Segregation analysis of the X-chromosome in a family with Rett syndrome in two generations

We report on the first family in which Rett syndrome (RTS) appeared in two consecutive generations. The index case is a 12-year-old girl (classical RTS); her maternal aunt, age 44 years, has mild RTS. Clinically, the family illustrates the wide phenotypic variability between cases, particularly in severity of neurological manifestations. We have analyzed the short arm of the X-chromosome of the family with gene technology. This did not uncover any genetic marker for diagnosis, but it did suggest how the syndrome might have segregated in the family. A cytogenetic analysis gave no information about chromosome abnormalities.     

Trisomy 21 mosaicism in two successive generations in a family.

The occurrence of 46,XX/47,XX,+21 mosaicism in two successive generations implies an aetiological relationship between the 47,XX,+21 cell line of the mother and her daughter.     

Larsen syndrome in two generations of an Italian family.

This paper describes a familial case of Larsen syndrome. Typical anomalies were present in the propositus and 2 of his 6 daughters. In addition, all patients had progressive deafness and the 2 daughters had cleft palate. The certain exclusion of any consanguinity between the couple, suggests, in this instance, the dominant mode of transmission of the syndrome.     

Four cases of omphalocele in two generations of the same family

A family in which four cases of omphalocele were found within two generations is presented. One of the patients also had Down's syndrome. To our knowledge, this is the first report of such an occurrence in one family.     

Aberrant axillary breast tissue: A report of a family with six affected women in two generations

A family with bilateral accessory axillary breasts without nipples or areolae in six adult females of two generations is reported. The anomaly is most likely caused by an autosomal dominant gene of variable expressivity which prevents normal regression of the embryonal mammary ridge. Accessory breasts with and without nipples and areolae have been seen in another family in the literature. In the absence of areolae or nipples the trait will usually be undetectable in prepubertal females and in males of all ages.     

Chagas disease in Mexico. Report of two acute cases

Two cases of acute Chagas disease in schoolchildren of 6 and 13 years of age, both with the clinical features of Roma?a's sign, regional lymphadenopathy, and fever, have a history of coexistence and the bite of the transmitter, and live in housing constructed with material considered at risk for infestation by the vector; i.e. roof and walls with palma/zacate (palm tree, grass leaves), dirt floor, and inadequate illumination and ventilation. The parasitological diagnosis of both cases was established by identification of trypomastigotes of Trypanosoma cruzi in blood smears and the parasite was isolated in one of them. Benznidazole treatment was administered according to the guidelines of the WHO/PAHO for this disease. The presence of acute Chagas disease in rural areas confirms the active transmission of the parasite, so surveillance and epidemiological controls should be applied. The importance of these cases is that T. cruzi infection is symptomatic in 5% of cases, which implies that a high percentage of cases of infection appear asymptomatic and are not being diagnosed in our country.     

Mutation analysis of an Ashkenazi Jewish family with Gaucher disease in three successive generations

Seven members of an Ashkenazi Jewish family with Gaucher disease in 3 successive generations were tested for the presence of the 2 common mutations known to occur in the glucocerebrosidase gene. Genomic DNA from blood or skin fibroblasts of relatives was amplified by using the PCR technique and individual mutations identified by oligonucleotides specific to the mutated sequences. Four individuals were homozygous for a mutation at amino acid 370 (370 mutation) known to occur only in type 1 disease. The other 3 affected relatives were compound heterozygotes for this mutation and for a mutation at amino acid 444 (NciI mutation) which, in the homozygous state, is associated with neurological disease. Clinical severity was more marked in the compound heterozygotes than in the homozygotes. Since the mutation is present in Ashkenazim, molecular diagnosis in families which carry the NciI mutation should prove useful in assessing their risk of the neurologic forms of Gaucher disease.     

Defective host defence mechanisms in a family with hypocalciuric hypercalcaemia and coexisting interstitial lung disease

An extensive in vitro investigation of the host defence system was performed in 11 sibs of a large kindred with unexplained combination of familial hypocalciuric hypercalcaemia (FHH), interstitial lung disease and increased susceptibility to respiratory infections. The impairment of host defence mechanism was most likely related to granulocyte dysfunction. A severe myeloperoxidase deficiency was the most consistent granulocyte defect (P less than 0.001) and it was associated with a relatively diminished chemiluminescence (P less than 0.001). Moreover, a significantly diminished antistaphylococcal phagocytic (P less than 0.001) and killing (P less than 0.001) activity was found which in the absence of any opsonizing defect implicates an intrinsic granulocyte dysfunction. We found no abnormalities in number of B and T lymphocytes nor in the balance between helper and suppressor cells determined with monoclonal antibodies. Despite the recurrent infections no elevations of the immunoglobulin subclasses were found. The relationship between the inherited FHH, interstitial lung disease and susceptibility to respiratory infections remains obscure. It is, however, clear that impairment of the host defence might contribute to a decreased life expectancy in this family.     

A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family

A sibship is reported of three generations of a Jordanian family of normal intelligence with a complex malformation of upper extremity, shoulder and thorax, which is combined with variously expressed congenital heart disease. The deformity consists of a flat glenoid fossa, a hypoplastic scapula, aplasia of the humerus and/or radius, bony spurs of the elbow joint and in the shoulder region, hypoplasia of the carpal joints and hypodactyly with aplasia of the thumb. The claviculae are short, thick and abnormally curved and there are kyphoscoliosis and pectus excavatum. Four siblings show congenital heart disease. Pelvis and lower extremity are normal. The condition is inherited as a Mendelian autosomal dominant.     

Oto-Palato-Digital syndrome in four generations of a larqe family

A new large family, affected by O-P-D syndrome is reported. Nine members in four consecutive generations have been studied. Computerized tomography study of spine and skull showed abnormalities to be confined to mesodermal derivates, while nervous structures were normal. Transmission pattern may be X-linked with intermediate expression in the female or autosomal dominant with sex limitation of expression.     

Chronic murine Chagas' disease: the impact of host and parasite genotypes

Chagas' disease is a protozoan infection caused by the flagellate Trypanosoma cruzi. Herein we utilise experimental infections of different mouse and parasite strains to investigate the relative importance of the host and parasite genotype, respectively, in causing Chagas' disease in mice. CBA/J and BALB/c mice infected with the Tulahuen strain of T. cruzi develop a severe acute disease characterised by transient parasitaemia and a high rate of mortality. While the acute phases in these mice are indistinguishable, they display differential outcomes of the infection since CBA/J mice eventually develop polymyositis and mild myocarditis whereas BALB/c mice are resistant to chronic disease. In contrast, BALB/c mice infected with the CA-1 clone of T. cruzi exhibit a mild acute phase, develop no polymyositis but do develop severe myocarditis. Thus both the parasite and host genotype, but not the severity of the acute phase, are important in determining the eventual outcome of T. cruzi infection. We also present a murine model suitable for investigating which host factors may be necessary to induce a chronic inflammatory disease after T. cruzi infection.     

The genetics of Crohn disease: complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives

We have analysed the pedigrees of 265 probands with Crohn disease, collected from a specialty clinic at the University of Düsseldorf. Complex segregation analysis suggests the presence of a recessive gene with incomplete penetrance for susceptibility to the disease with no residual causes of family resemblance. However, a proportion of the isolated cases are probably due to phenocopies, this proportion being greatest among cases with an advanced age of onset.     

An Indian family with postaxial Polydactyly in four generations

An Indian family was observed with postaxial Polydactyly in four generations. Of the twelve affected cases, eleven were male and one was female. The affected males showed postaxial Polydactyly Type A in both hands and feet. The affected female showed poly-syndactyly and both Types A and B postaxial Polydactyly. Study of this family strongly suggests a common causal factor for postaxial Polydactyly Types A and B and polysyndactyly. The observations also support an autosomal dominant pattern of inheritance and a high degree of genetic heterogeneity in this malformation.     

Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres

ObjectivesChagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole.MethodsThis was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)).Results471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p <0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08).ConclusionThe use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.