A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

The naturally occurring clonal diversity among field isolates of the major human malaria parasite Plasmodium vivax remained unexplored until the early 1990s, when improved molecular methods allowed the use of blood samples obtained directly from patients, without prior in vitro culture, for genotyping purposes. Here we briefly review the molecular strategies currently used to detect genetically distinct clones in patient-derived P. vivax samples, present evidence that multiple-clone P. vivax infections are commonly detected in areas with different levels of malaria transmission and discuss possible evolutionary and epidemiological consequences of the competition between genetically distinct clones in natural human infections. We suggest that, when two or more genetically distinct clones are present in the same host, intra-host competition for limited resources may select for P. vivax traits that represent major public health challenges, such as increased virulence, increased transmissibility and antimalarial drug resistance.

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections

Toxoplasmosis and ascaridiasis evoke polar Th-1 and Th-2 host immune responses, respectively. A study to investigate the specific cytokine profile production by in vitro cultures of peripheral blood mononuclear cells from individuals living under precarious sanitary conditions in a highly endemic area for the parasites Toxoplasma gondii and Ascaris lumbricoides was conducted. High levels of both IFN-³ (Th-1) and IL-13 (Th-2) were observed in groups of co-infected individuals presenting toxoplasmic ocular lesions. Significantly lower IL-10 and TGF-² levels were produced by co-infected individuals in comparison with groups of individuals not infected with A. lumbricoides and either positive or negative for T. gondii living under good sanitary conditions (control groups). The possible influence of co-parasitism on the clinical presentation of ocular toxoplasmosis is discussed.

Low frequency of human papillomavirus detection in prostate tissue from individuals from Northern Brazil

The presence of human papillomavirus (HPV) was evaluated in 65 samples of prostate tumours and six samples of prostates with benign prostatic hyperplasia from individuals from Northern Brazil. We used a highly sensitive test, the Linear Array HPV Genotyping Test, to detect 37 high and low-risk HPV types. In this study, only 3% of tumour samples showed HPV infection. Our findings support the conclusion that, despite the high incidence of HPV infection in the geographic regions studied, HPV was not associated with a higher risk of prostate cancer. To our knowledge, this is the first study evaluating the frequency of HPV detection in prostatic tissue of individuals from Brazil.

Frequency and types of human papillomavirus among pregnant and non-pregnant women with human immunodeficiency virus infection in Recife determined by genotyping

Women with human immunodeficiency virus (HIV) infection present a higher risk of infection by the human papillomavirus (HPV) and cervical cancer. To determine HPV genotypes and frequencies among HIV-positive women, an analytical cross-sectional study was carried out on 147 women (51 were pregnant and HIV-positive, 45 pregnant and HIV-negative and 51 HIV-positive and not pregnant), who were attended at a maternity hospital in Recife between April 2006-May 2007. They answered a questionnaire and underwent a gynaecological examination, with samples collected for HPV investigation by PCR, hybrid capture II, oncotic colpocytology (Papanicolau) and colposcopy. The frequency of HPV DNA was 85.3% (122/143), with a high proportion of HPV types that have been identified as high risk for cervical cancer. Among HIV-positive pregnant women, there was an HPV prevalence of 96% (48/50), of whom 60.4% (29/48) were high-risk. HPV 16, 58, 18, 66 and 31 were the most frequent types. Colpocytological abnormalities were observed in 35.3% (18/51) of HIV-positive non-pregnant women, 21.6% (11/51) of HIV-positive pregnant women and 13.3% (6/45) of HIV-negative pregnant women with a predominance of low-level lesions. A high prevalence of HPV infection was identified, especially with the high-risk types 16, 58, 18 and 66. This study identified high-risk HPV types in all three groups examined (HIV-positive pregnant women, HIV-negative pregnant women and HIV-positive not pregnant), characterising its distribution in this setting.

A Change in the Epidemiology of Infections Due to Extended-Spectrum b-Lactamase–Producing Organisms

Extended-spectrum β-lactamases (ESBLs) form a heterogeneous group that share the property of hydrolytic activity against the oxyimino-β-lactams while remaining susceptible to inhibition by β-lactamase inhibitors, such as clavulanic acid. From a clinical point of view, they are important because they confer resistance to penicillins, aztreonam, and cephalosporins, and ESBL-producing organisms are typically also resistant to aminoglycosides, trimethoprim-sulfamethoxazole, and quinolones [1]. Until recently, the main problem posed by ESBLs was related to nosocomial outbreaks caused by ESBL-producing Klebsiella species. These outbreaks are usually clonal, the strains are mainly spread through cross-transmission, and the risk factors are similar to those found for other multidrug-resistant nosocomial pathogens [2]. In Europe and the United States, most ESBL-producing Klebsiella isolates harbored enzymes belonging to the TEM and SHV families [3]. Detection of colonized patients by performing surveillance cultures within affected units, isolation precautions for colonized patients, and restriction of oxyimino-β-lactam use are frequently useful for the control of these outbreaks [1]. There is no evidence that hospital-acquired ESBL-producing klebsiellae are decreasing in importance—in fact, data from the Centers for Disease Control and Prevention show that 20.6% of Klebsiella pneumoniae isolates from United States intensive care units in 2003 were probable producers of ESBL [4]. This represented a 47% increase, compared with the preceding 5 years. However, during the last few years, an impressive increase in the number of ESBL-producing Escherichia coli (and, less frequently, other Enterobacteriaceae) is being described in several parts of the world [5–8]. This emergent phenomenon shows some differences from the problem posed by Klebsiella species; many of these ESBL-producing E. coli are isolated …

Risk factors associated with human papillomavirus infection in two populations from Rio de Janeiro, Brazil

We investigated human papillomavirus (HPV) infection in two female populations from diverse socio-economic strata from the state of Rio de Janeiro and we also investigated the possible co-factors related to infection and the progression to cancer. In Group I, the reference group of this study, 10.7% of the patients presented HPV infection, as detected by generic PCR, while in Group II (low socio-demographic conditions) HPV was detected in 31.1% of the samples. HPV16 was the most prevalent virus type found in both Groups I and II (5.3% and 10%, respectively), followed by HPV 18 (1.3% and 4.7%, respectively). Although only a small sample was analysed, we detected differences among the groups regarding the rates of HPV infection, HPV types, age, ethnicity, familial income, schooling, marital status, parity, tobacco smoking and oral contraceptive use. For Group I, the Papanicolaou test was the most powerful independent factor associated with HPV status, followed by an age of under 30 years old, the number of sexual partners and black ethnicity. Our data are in agreement with the co-factors that are typically described for the developed world. For Group II, the Pap test was also the most relevant variable that was analysed, but the history of other sexually transmitted diseases and the use of alcohol were additional factors that were implicated in infection. These findings point out the need for the development of general and specific strategies for HPV screening of all Brazilian women.

Relationship among epidemiological parameters of six childhood infections in a non-immunized Brazilian community

Epidemiological parameters, such as age-dependent force of infection and average age at infection () were estimated for rubella, varicella, rotavirus A, respiratory syncytial virus, hepatitis A and parvovirus B19 infections for a non-immunized Brazilian community, using the same sera samples. The for the aforementioned diseases were 8.45 years (yr) [95% CI: (7.23, 9.48) yr], 3.90 yr [95% CI: (3.51, 4.28) yr], 1.03 yr [95% CI: (0.96, 1.09) yr], 1.58 yr [95% CI: (1.39, 1.79) yr], 7.17 yr [95% CI: (6.48, 7.80) yr] and 7.43 yr [95% CI: (5.68, 9.59) yr], respectively. The differences between average ages could be explained by factors such as differences in the effectiveness of the protection conferred to newborns by maternally derived antibodies, competition between virus species and age-dependent host susceptibility. Our seroprevalence data may illustrate a case of the above-mentioned mechanisms working together within the same population.

Lung infections: the radiologist's perspective.

Imaging plays a key role in lung infections. A CT scan must be carried out when there is a strong clinical suspicion of pneumonia that is accompanied by normal, ambiguous, or nonspecific radiography, a scenario that occurs most commonly in immunocompromised patients. CT allows clinicians to detect associated abnormalities or an underlying condition and it can guide bronchoalveolar lavage or a percutaneous or transbronchial lung biopsy. An organism can vary in how it is expressed depending on the extent to which the patient is immunocompromised. This is seen in tuberculosis in patients with AIDS. The infective agents vary with the type of immune deficiency and some infections can quickly become life-threatening. Clinicians should be aware of the complex radiological spectrum of pulmonary aspergillosis, given that this diagnosis must be considered in specific settings.

The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives

In previous work, we proposed alternative protocols for following patients with treated Chagas disease and these are reviewed herein. Evidence was provided to support the following: (i) functional anti-trypomastigote antibodies are indicative of ongoing chronic Trypanosoma cruzi infections; (ii) specific antibodies detected by conventional serology (CS) with epimastigote extracts, fixed trypomastigotes or other parasite antigens may circulate years after parasite elimination; (iii) functional antibodies are evidenced by complement-mediated lysis of freshly isolated trypomastigotes, a test which is 100% specific, highly sensitive, and the first to revert after T. cruzi elimination and (iv) the parasite target for the lytic antibodies is a glycoprotein of high molecular weight (gp160) anchored at the parasite surface. The complement regulatory protein has been cloned, sequenced and produced as a recombinant protein by other groups and is useful for identifying functional anti-T. cruzi antibodies in ELISA tests, thus dispensing with the need for live trypomastigotes to manage treated patients. If used instead of CS to define cures for Chagas patients, ELISA will avoid unnecessary delays in finding anti-T. cruzi drugs. Other highly sensitive techniques for parasite DNA detection, such as PCR, need to be standardized and included in future protocols for the management of patients with drug-treated Chagas disease.

Infections after PRK could have a happy ending: a series of three cases.

BACKGROUND: Infectious keratitis after PRK remains a rare but potentially devastating complication. HISTORY AND SIGNS: Medical records of 3 male patients with infectious keratitis after uneventful PRK for myopia and astigmatism were reviewed retrospectively. PRK was performed using the Wavelight Allegretto excimer laser. Postoperative care included a bandage contact lens (BCL) for 5 days, topical antibiotics, ketorolac, and artificial tears. THERAPY AND OUTCOME: Keratitis presented 2 - 4 days postoperatively. In one case, each culture was negative (case 1), and was positive for Streptococcus pneumoniae (case 2) and Staphylococcus aureus (case 3). Final BSCVA (best spectacle corrected visual acuity) after intensive antibiotic treatment and removal of BCL were 1.0 (case 1), 0.9 (case 2) and 0.3 correctable to 0.8 with pinhole (case 3). CONCLUSIONS: Postoperative broad-spectrum antibiotics are mandatory after PRK to prevent infectious keratitis. However, resistant organisms are more and more common. The presence of a bandage soft contact lens after surgery is an unfavourable element that may increase risk of infection. Based on our case series, we suggest limiting soft contact lens wear during the two postoperative days even if the corneal ulceration is not healed.

Comparison of HPV genotyping by type-specific PCR and sequencing

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and there is a strong link between certain high-risk viral types and cervical carcinogenesis. Although there are several typing methods, it is still unclear which test is the best. This study compared the effectiveness of type-specific PCR (TS-PCR) and sequencing, with a focus on their clinical application. A total of 260 cervical samples from HPV-positive patients were tested for types 6, 11, 16, 18, 31, 33 and 35 using TS-PCR and sequencing. The genotype was identified in 36% of cases by TS-PCR and in 75% by sequencing. Sequencing was four times more likely to identify the viral type in positive samples than TS-PCR (p = 0.00). Despite being more effective for virus genotyping, sequencing was unable to identify viral types in multiple infections. Combining both techniques resulted in highly sensitive detection (87% of cases), showing that they are complementary methods. HPV genotyping is an important step in HPV management, helping to identify patients with a higher risk of developing cervical cancer and contributing to the development of type-specific vaccines.

Assessing protein stability of the dimeric DNA-binding domain of E2 human papillomavirus 18 with molecular dynamics

The objective of this study is to understand the structural flexibility and curvature of the E2 protein of human papillomavirus type 18 using molecular dynamics (6 ns). E2 is required for viral DNA replication and its disruption could be an anti-viral strategy. E2 is a dimer, with each monomer folding into a stable open-faced β-sandwich. We calculated the mobility of the E2 dimer and found that it was asymmetric. These different mobilities of E2 monomers suggest that drugs or vaccines could be targeted to the interface between the two monomers.

High prevalence and low E6 genetic variability of human papillomavirus 58 in women with cervical cancer and precursor lesions in Southeast Mexico

Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer (CC). Throughout the world, HPV type 58 prevalence varies from one region to another; it is higher in women from certain countries in Asia and Latin America, such as China and Mexico. Although intratypic variants have been reported on a few occasions, our knowledge about HPV 58 genetic variation remains limited. Therefore, this work aims to (i) determine the prevalence of HPV type 58 amongst Mexican women with invasive CC or precursor lesions and (ii) identify HPV 58 sequence variants. One hundred and forty five colposcopy clinic patients were studied. Genotyping of HPV 16, 18 and 58 was determined by specific nested PCR and HPV 58 variants were detected by direct sequencing. The general prevalence of HPV was 51.7% (75/145). HPV 16 was found in 30.6% (23/75) and HPV 58 in 24% (18/75) of the patients. HPV 18 was not identified in patients with cervical intraepithelial neoplasia (CIN) grade I; it was only found in those with CIN II, with a prevalence of 6.8% (3/44). In patients with CC, the prevalence of HPV 16 and 58 was 78.9%. Regarding HPV 58 variants, 94.4% of the HPV 58 sequences were identical to the prototype strain, whereas one sample showed changes at a single nucleotide. This study demonstrates a high prevalence of HPV 58 and a low genetic variability of E6 sequences amongst Mexican colposcopy patients.

Infections cutanées causées par des mycobactéries à croissance rapide [Skin infections due to rapid-growing mycobacteria].

Rapid-growing mycobacteria (e.g. M. abscessus and M. chelonae) are emerging pathogens with various clinical manifestations. Among immunocompetent individuals, rapid-growing mycobacteria may be responsible of pulmonary, cutaneous, osteoarticular and postoperative infections, as well as lymphadenitis and catheter-associated infections. Among immunocompromised patients, disseminated infections are also observed. Diagnosis relies on specific microbiological investigations to confirm etiology and guide antibiotic treatment. The treatment requires a multi-disciplinary approach that includes specific long-term antibiotic treatment, surgical debridement and reduction of immunosuppression whenever possible.

Control of Mycobacterium fortuitum and Mycobacterium intracellulare infections with respect to distinct granuloma formations in livers of BALB/c mice

Mycobacterium fortuitum is a rapidly growing nontuberculous Mycobacterium that can cause a range of diseases in humans. Complications from M. fortuitum infection have been associated with numerous surgical procedures. A protective immune response against pathogenic mycobacterial infections is dependent on the granuloma formation. Within the granuloma, the macrophage effector response can inhibit bacterial replication and mediate the intracellular killing of bacteria. The granulomatous responses of BALB/c mice to rapidly and slowly growing mycobacteria were assessed in vivo and the bacterial loads in spleens and livers from M. fortuitum and Mycobacterium intracellulare-infected mice, as well as the number and size of granulomas in liver sections, were quantified. Bacterial loads were found to be approximately two times lower in M. fortuitum-infected mice than in M. intracellulare-infected mice and M. fortuitum-infected mice presented fewer granulomas compared to M. intracellulare-infected mice. These granulomas were characterized by the presence of Mac-1+ and CD4+ cells. Additionally, IFN-γmRNA expression was higher in the livers of M. fortuitum-infected mice than in those of M. intracellulare-infected mice. These data clearly show that mice are more capable of controlling an infection with M. fortuitum than M. intracellulare. This capacity is likely related to distinct granuloma formations in mice infected with M. fortuitum but not with M. intracellulare.