Efficience of human Plasmodium falciparum malaria vaccine candidates in Aotus lemurinus monkeys

The protective efficacy of several recombinat and a synthetic Plasmodium falciparum protein was assessed in Aoutus monkeys. The rp41 aldolase, the 190L fragment of the MSA-1 protein and fusion 190L-CS. T3 protein containg the CS. T3 helper "universal epitope were emulsified in Freund's adjuvants and injected 3 times in groups of 4-5 monkeys each one. The synthetic polymer Spf (66)30 also emulsified in Freund's adjuvants was injected 6 times. Control groups for both experiments were immunized with saline solution in the same adjuvant following the same schedules. Serology for malaria specific antibodies showed seroconversion in monkeys immunized with the recombinant proteins but not in those immunized with the polymer nor in the controls. Challenge was performed with the 10 (elevado a quinta potência) parasites from the P. falciparum FVO isolate. Neither rp41 nor SPf (66)30 induced protection, whereas 190L induced significant delay of parasitemia. The fusion of the CS. T3 epitope to 190L significantly increased is protective capacity.

Modern immunological approaches to assess malaria transmission and immunity and to diagnose plasmodial infection

The present paper reviews our recent data concerning the use of immunological methods employing monoclonal antibodies and synthetic peptides to study malaria transmission and immunity and to diagnose plasmodial infection. As concerns malaria transmission, we studied the main vectors of human malaria and the plasmodial species transmitted in endemic areas of Rondônia state, Brazil. The natural infection on anopheline was evaluated by immunoradiometric assay (IRMA) using monoclonal antibodies to an immunodominant sporozoite surface antigen (CS protein) demonstrated to be species specific. Our results showed that among six species of Anopheles found infected, An. darlingi was the main vector transmitting Plasmodium falciparum and P. vivax malaria in the immediate vicinity of houses. In order to assess the level of anti-CS antibodies we studied, by IRMA using the synthetic peptide corresponding to the repetitive epitope of the sporozoite CS protein, sera of individuals living in the same areas where the entomological survey has been performed. In this assay the prevalence of anti-CS antibodies was very low and did not reflect the malaria transmission rate in the studied areas. In relation to malaria diagnosis, a monoclonal antibody specific to an epitope of a 50 kDa exoantigen, the major component of supernatant collected at the time of schizont rupture, was used as a probe for the detection of P. falciparum antigens. This assay seemed to be more sensitive than parasitological examination for malaria diagnosis since it was able to detect plasmodial antigens in both symptomatic and asymtomatic individuals with negative thick blood smear at different intervals after a last parasitologically confirmed confirmed attack of malaria.

Antibodies anti Bloodstream and Circumsporozoite Antigens (Plasmodium vivax and Plasmodium malariae/P. brasilianum) in Areas of Very Low Malaria Endemicity in Brazil

During 1992-1994, 33 malaria cases were reported in two regions in Brazil where few sporadic atypical cases occur, most of them in home owners, who are weekenders, while home caretakers live there permanently. Indirect Fluorescent Antibody Test (IFAT), with Plasmodium vivax, and Enzime Linked Immunosorbent Assay (ELISA) with repeat peptides of the circumsporozoite (CS) proteins of the 3 known P. vivax variants and P. malarie/P. brasilianum, were performed on 277 sera, obtained within a 5 to 10 km range of malaria cases. Very rarely did any of these donors recall typical malaria episodes. Blood smears of all but 5 were negative. One of the 5 malaria cases included in our serology was of a home owner, 1 of a permanent resident, 3 from Superintendência de Controle de Endemias employees who went there to capture mosquitoes. In Region 1 the prevalence of IFAT positive sera was 73% and 28% among caretakers, 18% and 9.6% among home owners. In Region 2 (3 localities) no distinction was possible between caretakers and home owners, IFAT positivity being 38%, 28% and 7%. The relative percentage of positive anti-CS repeats ELISA, differed for each of the peptides among localities. Dwellings are in the vicinity of woods, where monkeys are frequently seen. The origin of these malaria cases, geographical differences and high seropositivity is discussed

Coinfection by Strongyloides stercoralis in blood donors infected with human T-cell leukemia/lymphoma virus type 1 in São Paulo city, Brazil

The frequency of coinfection with Strongyloides stercoralis and human T-cell leukemia/lymphoma virus type 1 (HTML-1) was determined in 91 blood donors examined at the blood bank of a large hospital in São Paulo city, Brazil. As control group 61 individuals, not infected by HTLV-1, were submitted to the same techniques for the diagnosis of S. stercoralis infection. In HTLV-1 infected patients the frequency of S. stercoralis infection was 12.1%; on the other hand, the control group showed a frequency significantly lower of S. stercoralis infection (1.6%), suggesting that HTLV-1 patients shoud be considered as a high risk group for strongyloidiasis in São Paulo city.

First report of Lutzomyia (Nyssomyia) umbratilis Ward & Frahia, 1977 outside of Amazonian Region, in Recife, State of Pernambuco, Brazil (Diptera: Psychodidae: Phlebotominae)

Lutzomyia umbratilis, a known vector of Leishmania guyanensis in the north of Amazon basin, has been exclusively found in the Amazonian region. Here we report for the first time the occurrence of this species in northeastern Brazil. The epidemiological importance of the occurrence of this species in the Atlantic Forest is commented.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74%). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87%), and 16 (70%) were unable to walk. All individuals presented urinary retention and 19 (83%) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22%) presented a full response to treatment, 13 (57%) partial response without functional limitations and 4 (17%) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement.

Antimicrobial susceptibility determined by the E test, Löwenstein-Jensen proportion, and DNA sequencing methods among Mycobacterium tuberculosis isolates discrepancies, preliminary results

Mycobacterium tuberculosis strains resistant to streptomycin (SM), isoniazid (INH), and/or rifampin (RIF) as determined by the conventional Löwenstein-Jensen proportion method (LJPM) were compared with the E test, a minimum inhibitory concentration susceptibility method. Discrepant isolates were further evaluated by BACTEC and by DNA sequence analyses for mutations in genes most often associated with resistance to these drugs (rpsL, katG, inhA, and rpoB). Preliminary discordant E test results were seen in 75% of isolates resistant to SM and in 11% to INH. Discordance improved for these two drugs (63%) for SM and none for INH when isolates were re-tested but worsened for RIF (30%). Despite good agreement between phenotypic results and sequencing analyses, wild type profiles were detected on resistant strains mainly for SM and INH. It should be aware that susceptible isolates according to molecular methods might contain other mechanisms of resistance. Although reproducibility of the LJPM susceptibility method has been established, variable E test results for some M. tuberculosis isolates poses questions regarding its reproducibility particularly the impact of E test performance which may vary among laboratories despite adherence to recommended protocols. Further studies must be done to enlarge the evaluated samples and looked possible mutations outside of the hot spot sequenced gene among discrepant strains.

Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure

The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5% malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population.The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5% malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.

Spatial distribution of schistosomiasis foci on Itamaracá Island, Pernambuco, Brazil

Acute cases of schistosomiasis have been found on the coastal area of Pernambuco, Brazil, due to environmental disturbances and disorderly occupation of the urban areas. This study identifies and spatially marks the main foci of the snail host species, Biomphalaria glabrata on Itamaracá Island. The chaotic occupation of the beach resorts has favoured the emergence of transmission foci, thus exposing residents and tourists to the risk of infection. A database covering five years of epidemiological investigation on snails infected by Schistosoma mansoni in the island was produced with information from the geographic positioning of the foci, number of snails collected, number of snails tested positive, and their infection rate. The spatial position of the foci were recorded through the Global Positioning System (GPS), and the geographical coordinates were imported by AutoCad. The software packages ArcView and Spring were used for data processing and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and areas of environmental risk were identified and spatially analyzed allowing the identification of the areas exposed to varying degrees of risk.

Intracellular polyamine pools, oligopeptide-binding protein A expression, and resistance to aminoglycosides in Escherichia coli

The role of intracellular free polyamine (putrescine and spermidine) pools in multiple resistance to aminoglycoside antibiotics was investigated among in vitro selected kanamycin-resistant Escherichia coli J53 mutants expressing diminished oligopeptide-binding protein (OppA) levels and/or defective ornithine decarboxylase (ODC) activity. The results suggest that diminished OppA content, but not defective ODC activity expression, increased the relative concentration of free spermidine as compared to the wild type strain. Moreover, by adding exogenous polyamines or polyamine synthesis inhibitors to cultures with different mutant strains, a direct relationship between the intracellular OppA levels and resistance to kanamycin was revealed. Collectively these results further suggest a complex relation among OppA expression, aminoglycoside resistance and polyamine metabolism.

Detection of dengue virus serotype 3 by reverse transcription-polymerase chain reaction in Aedes aegypti (Diptera, Culicidae) captured in Manaus, Amazonas

The detection of dengue virus serotypes from Aedes aegypti in Manaus, state of Amazonas was carried out using the reverse transcription-polymerase chain reaction technique. Fourteen pools out 82 (17.1%) were positive for DENV3, providing a minimal infection rate of 2.1% of all analyzed infected female specimens of three different areas of the city.

Local anaesthetic medication for the treatment of asthma

It is presumed that drugs able to prevent bronchial spasm and/or inflammation may have therapeutic potential to control asthma symptoms. The local anaesthetic lidocaine has recently received increased attention as an alternative form of treatment for asthmatic patients. This paper reviews the major findings on the topic and summarizes the putative mechanisms underlying the airway effects of local anaesthetic agents. We think that lidocaine extends the spectrum of options in asthma therapy, probably by counteracting both spasmogenic and inflammatory stimuli in the bronchial airways. The possibility of development of new anti-asthma compounds based on the synthesis of lidocaine derivatives is also on the horizon.

Characterization of the gene expression related to the process of DNA damage tolerance in Schistosoma mansoni

In the course of its complex life cycle, the parasite Schistosoma mansoni need to adapt to distinct environments, and consequently is exposed to various DNA damaging agents. The Schistosoma genome sequencing initiative has uncovered sequences from genes and transcripts related to the process of DNA damage tolerance as the enzymes UBC13, MMS2, and RAD6. In the present work, we evaluate the importance of this process in different stages of the life cycle of this parasite. The importance is evidenced by expression and phylogenetic profiles, which show the conservation of this pathway from protozoa to mammalians on evolution.

Disagreement between ultrasound and magnetic resonance imaging in the identification of schistosomal periportal fibrosis

Abdominal ultrasound (US) has been widely used in the evaluation of patients with schistosomiasis mansoni. It represents an important indirect method of diagnosis and classification of the disease, and it has also been used as a tool in the evaluation of therapeutic response and regression of fibrosis. We describe the case of a man in whom US showed solid evidence of schistosomal periportal fibrosis and magnetic resonance imaging revealed that periportal signal alteration corresponded to adipose tissue which entered the liver togheter with the portal vein.

Vector bionomics and malaria transmission in the Upper Orinoco River, Southern Venezuela

A longitudinal epidemiological and entomological study was carried out in Ocamo, Upper Orinoco River, between January 1994 and February 1995 to understand the dynamics of malaria transmission in this area. Malaria transmission occurs throughout the year with a peak in June at the beginning of the rainy season. The Annual Parasite Index was 1,279 per 1,000 populations at risk. Plasmodium falciparum infections accounted for 64% of all infections, P. vivax for 28%, and P. malariae for 4%. Mixed P. falciparum/P. vivax infections were diagnosed in 15 people representing 4% of total cases. Children under 10 years accounted for 58% of the cases; the risk for malaria in this age group was 77% higher than for those in the greater than 50 years age group. Anopheles darlingi was the predominant anopheline species landing on humans indoors with a biting peak between midnight and dawn. A significant positive correlation was found between malaria monthly incidence and mean number of An. darlingi caught. There was not a significant relationship between mean number of An. darlingi and rainfall or between incidence and rainfall. A total of 7295 anophelines were assayed by ELISA for detection of Plasmodium circumsporozoite (CS) protein. Only An. darlingi (55) was positive for CS proteins of P. falciparum (0.42%), P. malariae (0.25%), and P. vivax-247 (0.1%). The overall estimated entomological inoculation rate was 129 positive bites/person/year. The present study was the first longitudinal entomological and epidemiological study conducted in this area and set up the basic ground for subsequent intervention with insecticide-treated nets.