Henrique Krieger

Mannan-Binding Lectin Enhances Susceptibility to Visceral Leishmaniasis

ABSTRACT Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with the probability of developing visceral leishmaniasis. Monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of tumor necrosis factor alpha and interleukin-6 than cells infected with nonopsonized parasites. Our findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.

The epidemiology of malaria in Rondonia (Western Amazon region Brazil): study of a riverine population.

We report on a longitudinal study concerning the incidence of malaria in a riverine population (Portuchuelo) settled on the riverbanks of Rio Madeira, in the State of Rondonia, Brazil. We found the incidence of malaria to be seasonal, prevailing in the dry months of June and July. The Annual Parasite Index (API) was 292/1000 inhabitants, almost three times that of the state of Rondonia for the same period. In contrast with other studied Rondonian populations, malaria in Portuchuelo was more prevalent in youngsters < 16 years old, particularly in the 0-1 year age group. Adults were relatively spared, particularly those over 50 years. Besides being indicative of indoor transmission, these facts may suggest the existence of a certain degree of acquired resistance to infection and/or of lessened symptoms in older people. Riverine populations are spread over the entire Amazon region where most of its members were born. Due to the permanent presence of malaria among riverine populations, we are proposing that they may act as perennial reserves of malaria and, therefore, as sources of infection for migrants or eventual settlers at their vicinity. To date, the opposite view has been generally held. Anopheles darlingi, the main vector species in the area, is essentially sylvatic, which contributes to make the control of malaria highly problematic. The only hopes for control rest on permanent surveillance and the prompt treatment of patients, which are also problematic considering the vastness of the Amazon region and the remoteness of some of its riverine settlements.

Major Gene and Multifactorial Inheritance of Mandibular Prognathism

Mandibular prognathism typically shows familial aggregation. Various genetic models have been described and it is assumed to be a multifactorial and polygenic trait, with a threshold for expression. Our goal was to examine specific genetic models of the familial transmission of this trait. The study sample comprised of 2,562 individuals from 55 families. Complete family histories for each proband were ascertained and the affection status of relatives were confirmed by lateral cephalograms, photographs, and dental models. Pedigrees were drawn using PELICAN and complex segregation analysis was performed using POINTER. Parts of some pedigrees were excluded to create one founder pedigrees, so the total N was 2,050. Analysis showed more affected females than males (P = 0.030). The majority of the pedigrees suggest autosomal dominant inheritance. Incomplete penetrance was demonstrated by the ratio of affected/unaffected parents and siblings. The heritability of mandibular prognathism was estimated to be 0.316. We conclude that there is a major gene that influences the expression of mandibular prognathism with clear signs of Mendelian inheritance and a multifactorial component.

The association of genetic markers and malaria infection in the Brazilian Western Amazonian region

Almost all individuals (182) belonging to an Amazonian riverine population (Portuchuelo, RO, Brazil) were investigated for ascertaining data on epidemiological aspects of malaria. Thirteen genetic blood polymorphisms were investigated (ABO, MNSs, Rh, Kell, and Duffy systems, haptoglobins, hemoglobins, and the enzymes glucose-6-phosphate dehydrogenase, glyoxalase, phosphoglucomutase, carbonic anhydrase, red cell acid phosphatase, and esterase D). The results indicated that the Duffy system is associated with susceptibility to malaria, as observed in other endemic areas. Moreover, suggestions also arose indicating that the EsD and Rh loci may be significantly associated with resistance to malaria. If statistical type II errors and sample stratification could be ruled out, hypotheses on the existence of a causal mechanism or an unknown closely linked locus involved in susceptibility to malaria infection may explain the present findings.

Genetic causes involved in Leishmania Chagasi infection innortheastern: Brazil

A sample of 502 individuals from 94 families from Jacobina, State of Bahia, Brazil, was investigated to determine the causal mechanisms involved in Leishmania chagasi (the causal agent of visceral leishmaniasis in the American hemisphere) infection, as measured by the intradermic reaction to antigens derived from this parasite, using complex segregation analyses. The results showed evidence of a major genetic mechanism acting on infection, with a frequency of a recessive (or additive) susceptibility gene (q) of approximately 0.45. A small multifactorial component (H = 0.29) acting in conjunction with a major recessive gene (q = 0.37) is not ruled out as a concomitant causative factor.

Malaria control in an agro-industrial settlement of Rondônia (Western Amazon region, Brazil).

A malaria control pilot project was developed in the Urupá agro-industrial farm that is situated in the State of Rondônia (Western Amazon Region, Brazil). Around 180 inhabitants had been surveyed for the past five years. The control measures were based on (1) training a community agent to perform on the spot microscopical diagnosis of malaria and to treat the uncomplicated cases of malaria; (2) limiting the use of insecticides to a short period before the high transmission season. This resulted in a significant reduction in the time between the onset of clinical symptoms and specific chemotherapy which fell from 3.5 to 1.3 days. In relation to the previous three reference years the total number of malaria cases was reduced to 50% in the first year and to 25% in the second year. The introduction of these measures coincided with pronounced reduction in the frequency of Plasmodium falciparum infections but this was less marked for P. vivax infections. In the second year of the pilot experiment there was no P. falciparum transmission on the farm. During the last decade there was a general decrease in the endemicity of malaria in the State of Rondônia. The linear regression coefficient values indicate that the decline was more pronounced in Urupá than in the general municipality and that the falciparum malaria API in Urupá farm is significantly lower than in the general municipality of Candeias were the farm is situated.

Genetic and environmental determinants of 17 serum biochemical traits in Brazilian twins

The genetic and environmental effects on the levels of 17 serum biochemical quantitative traits (calcium, phosphorus, glucose, urea nitrogen, uric acid, total protein, albumin, total bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH), glutamic-oxaloacetic transaminase (SGOT), total lipid, cholesterol, triglyceride, alpha-lipoprotein, pre-beta-lipoprotein and beta-lipoprotein) were estimated in 105 pairs of healthy twins of both sexes (57 MZ and 48 DZ) by path analysis. The genotype effect h2 was significant for all traits (P less than 0.001) and its value extended from 0.52 (alpha-lipoprotein) to 0.81 (alkaline phosphatase), whereas environmental effect b2 was significant (P less than 0.05) in only 10 traits of the 17 analyzed, with the maximum value of 0.13 (cholesterol). Correlations between genotypes of paired traits were estimated and, of 136 values, 47 were significant at the 5% levels, thus indicating partial and common genetic mechanisms.

Genetic Epidemiology of the Mitsuda Reaction in Leprosy

This study comprised 544 nuclear families with 2,925 individuals tested for the Mitsuda reaction, from the Campinas region in Brazil. Segregation analyses suggest the segregation of a major gene (chi 2(1) = 0.07 - 0.07 = 0, p = 1), by failing to reject the hypothesis of Mendelian transmission and by rejecting the hypothesis of nontransmission of a major gene (chi 2(3) = 0.07 - 0.0 = 0.07, p > 0.99; chi 2(2) = 198.28 - 0.0 = 198.28, p < 0.0001).

Glutathione S-Transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms in a Brazilian Mixed Population

The GSTM1 and GSTT1 null genotype frequencies were significantly different between 658 nonblack and black healthy blood donors from a Brazilian mixed population (Rio de Janeiro). The GSTM1 phenotype distribution was not in Hardy–Weinberg equilibrium in either group, mainly because of an excess of the GSTM1*A/*B genotype.

Birth weight of twins: 1. The fetal growth patterns of twins and singletons

As distribuicoes dos pesos de recem-nascidos de partos gemelares e unicos em tres maternidades do sudeste brasileiro foram comparadas, depois do ajustamento desses pesos a idade gestacional, seus termos quadratico e cubico, sexo e tipo de gestacao e as interacoes dessas variaveis. O padrao da taxa de crescimento fetal dos gemeos em comparacao ao dos recem-nascidos de parto unico e retardado, independentemente do nivel socio-economico da populacao examinada, mas a idade gestacional em que comeca esse atraso parece estar correlacionada ao nivel economico das maes. Em todos os casos, depois de 28 semanas de gestacao, o crescimento dos fetos femininos mostrou-se levemente, mas consistentemente, inferior ao dos fetos masculinos.