Malaria: burden of disease.

Despite more than 100 years since Laveran described plasmodium species and Ross confirmed that they were transmitted by female anopheline mosquitoes, malaria remains a leading cause of morbidity and mortality worldwide. Although the areas where transmission takes place have reduced, and they are by now confined to the inter tropical areas, the number of people living at risk has grown to about 3 billion, and is expected to go on increasing. Not only does malaria cause around 500 million cases every year, and between 1 and 3 million deaths, but it also carries a huge burden that impairs the economic and social development of large parts of the planet. The failed attempt to eradicate malaria gave way to the control policy that was followed by a huge resurgence of malaria during the late 70s and 80s. Together with the emergence and spread of resistance to chloroquine and the weak health infrastructure in many of the endemic countries, particularly in Africa, the malaria situation worsened worldwide. The last decade of the 20th century was witness to the international community becoming increasingly aware of the unacceptable situation that the burden of malaria represented to large parts of the world. Renewed efforts to describe the problem, design and evaluate new control strategies, design and develop new drugs, better understand the biology of the parasite and the immunity it induces in the human host, develop candidate vaccines, together with new financial support constitute renewed hope that may lead to new trends in global health.

Analysis of the mechanisms of resistance to several antimicrobial agents in Shigella spp. causing travellers' diarrhoea.

Eighty isolates of Shigella spp. (37 Shigella flexneri and 43 Shigella sonnei) from patients with travellers' diarrhoea were studied. Susceptibility tests revealed high levels of resistance, especially to ampicillin (65%), tetracycline (78%) and trimethoprim (75%), and particularly among the S. flexneri isolates. Dihydrofolate reductase 1 genes (dfrA1) were prevalent among the trimethoprim-resistant isolates, while oxa genes predominated among the ampicillin-resistant isolates. Chloramphenicol resistance was associated with production of chloramphenicol acetyltransferase, while nalidixic acid-resistant isolates had a single mutation in the gyrA gene. The results indicate a continuing need for resistance surveillance and rational use of antimicrobial agents.

Genetic diversity of Shigella species from different intercontinental sources.

One hundred and twenty three strains of Shigella spp. (mostly Shigella sonnei and Shigella flexneri) were isolated between 1995 and 2000 from patients suffering from traveller's diarrhoea. Seventy nine of them have been typed by digestion of their chromosomal DNA with Xba I and pulsed field gel electrophoresis. Results show a high degree of heterogeneity in both S. sonnei and S. flexneri isolates. This is the first time that the molecular typing of such a high number of geographically unrelated isolates of Shigella sp. is carried out, showing a high level of genomic re-arrangement.

Molecular characterization of the integrons in Shigella strains isolated from patients with traveler's diarrhea.

The prevalence and characterization of Class 1 integrons has been performed in eighty three strains of Shigella spp., isolated between 1995 and 2000 from patients with traveler's diarrhea. A low prevalence (13.25%) was recorded. Nine different integrons were found among 11 multiresistant strains, with a total of 10 different gene cassettes encoding for resistance to trimethoprim (dfrA1, dfrA5, dfrA7, dfrA12, and dfrA15), aminoglycosides (aadA1a and aadA2), beta-lactam antibiotics (oxa2) or ORF with unknown function (orfD and orfF). A high prevalence of dfr and aad gene cassettes was observed. The low incidence of Class 1 integrons observed in this study is in contrast with the known facility that the Shigella genus has to gain and transfer plasmids.

Integron-mediated antibiotic multiresistance in Acinetobacter baumannii clinical isolates from Spain.

OBJECTIVE: To determine whether non-epidemiologically related, antibiotic-resistant isolates of Acinetobacter baumannii from different geographical origins possess common type 1 integrons. METHODS: The epidemiologic relationships between seven A. baumannii strains recovered from different Spanish hospitals were established by pulsed-field gel electrophoresis, the presence of integrons being determined by PCR and DNA sequencing. RESULTS: Integron analysis showed the presence of four different integrons, containing six different known genes (aacC1, aacA4, aadA1, aadB, oxa21 and oxa37) plus an ORF. It was found that the same integron was present in different unrelated strains and that related strains could have different integrons. CONCLUSION: These results show the potential risk of integron dissemination among different strains of A. baumannii.

Analysis of the mechanisms of quinolone resistance in clinical isolates of Citrobacter freundii.

The presence of gyrA, gyrB and/or parC mutations, quinolone uptake, outer membrane protein profiles and epidemiological relationship were studied in 12 clinical isolates of Citrobacter freundii. No alterations were observed in the gyrB gene of any of the strains, or gyrA or parC of the four quinolone-susceptible strains (nalidixic acid MIC of 2-4 mg/L, and a ciprofloxacin MIC of 0.006-0.06 mg/L). The quinolone-resistant strains were classified into two groups: one group (group A) composed of strains resistant to nalidixic acid but not to ciprofloxacin and another (group B) including those resistant to both antibiotics with a mutation at codon 83 of the gyrA gene (Thr-->Ile), but no alteration in either parC or gyrB genes. In group B, three of the four resistant isolates, with a nalidixic acid MIC > 1024 mg/L and ciprofloxacin MIC of 8-32 mg/L, showed concomitant mutations at codons 83 and 87 of the gyrA gene (Thr-->Ile and Asp-->Tyr, respectively) as well as a single mutation in codon 80 of the parC gene (Ser-->Ile). The fourth isolate did not possess the mutation at codon 87 of gyrA. Two strains belong to the same clone and, although they had the same type of mutations in the gyrA and parC genes, showed different MICs of ciprofloxacin. This difference was related to an efflux pump mechanism. Mutations in the gyrA and parC genes play the main role in quinolone resistance development in Citrobacter freundii, although other factors such as overexpression of efflux pumps can play a complementary role and thus modulate the final quinolone MIC.

Typing and characterization of mechanisms of resistance of Shigella spp. isolated from feces of children under 5 years of age from Ifakara, Tanzania.

Eighty-six strains of Shigella spp. were isolated during the dry season from stool samples of children under 5 years of age in Ifakara, Tanzania. The epidemiological relationship as well as the antimicrobial susceptibility and mechanisms of resistance to ampicillin, chloramphenicol, and co-trimoxazole were investigated. Four different epidemiological tools, pulsed-field gel electrophoresis (PFGE), repetitive extragenic palindromic (REP)-PCR, plasmid analysis, and antibiogram, were compared for typing Shigella strains. Seventy-eight (90%) strains were Shigella flexneri and were distributed into four groups, by either PFGE or REP-PCR, with 51, 17, 7, and 3 strains. The four strains of Shigella dysenteriae belonged to the same group, and the four strains of Shigella sonnei were distributed in two groups with three and one strain each. Plasmid analysis showed a high level of heterogeneity among strains belonging to the same PFGE group, while the antibiogram was less discriminative. REP-PCR provided an alternative, rapid, powerful genotyping method for Shigella spp. Overall, antimicrobial susceptibility testing showed a high level of resistance to ampicillin (81.8%), chloramphenicol (72.7%), tetracycline (96.9%), and co-trimoxazole (87.9%). Ampicillin resistance was related to an integron-borne OXA-1-type beta-lactamase in 85.1% of the cases and to a TEM-1-type beta-lactamase in the remaining 14.8%. Resistance to co-trimoxazole was due to the presence of a dhfr Ia gene in all groups except one of S. flexneri, where a dhfr VII gene was found within an integron. Chloramphenicol resistance was associated in every case with positive chloramphenicol acetyltransferase activity. All strains were susceptible to nalidixic acid, ciprofloxacin, ceftazidime, cefotaxime, and cefoxitin. Therefore, these antimicrobial agents may be good alternatives for the treatment of diarrhea caused by Shigella in Tanzania.

Molecular evidence of mother-to-infant transmission of hepatitis G virus among women without known risk factors for parenteral infections.

Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known risk factors for HGV infection and in 7 of 18 children born to HGV RNA-positive mothers. Molecular evidence of mother-to-infant transmission was obtained only for three of seven children. HGV RNA was also detected in 4 of 42 children born to non-HGV-infected women. Thus, mechanisms other than materno-filial may play an important role in HGV transmission during early childhood.