Evaluation of a peer intervention project in the hospital setting to improve the health-related quality of life of recently diagnosed people with HIV infection.

PURPOSE: This study aims to assess the impact of a peer intervention programme in the hospital setting to improve the health-related quality of life (HRQoL) of people recently diagnosed with HIV infection. METHODS: A quasi-experimental single-group study with pre- and post-measurements was conducted. The peer intervention programme consisted of four sessions that took place at the following times: (1) the day of diagnosis, (2) the day when the results of the analyses were collected and ART (antiretroviral therapy) began, (3) one month after the start of ART, and (4) four months after the start of ART. The dependent variables were HRQoL and several of its psychological predictors. Change in the dependent variables was analysed through repeated measures, variance analysis and covariance analysis. Forty-three people with HIV participated in the intervention (40 men, mean age = 39.14). RESULTS: A significant positive evolution was found in all the predictors of HRQoL, except avoidant coping (p < .05). A positive evolution was also found in all HRQoL dimensions (p < .05). There was a significant increase in CD4 cells/mm3 lymphocytes (p < .0001) and in the CD4/CD8 ratio (p < .001). The positive differential scores in the psychological health and social relationship dimensions influenced the increase in CD4 cells/mm3 lymphocytes (p = .012, p = .13). The increase in the social relations dimension score and overall health perception influenced the recovery of the CD4/CD8 ratio (p = .044; p = .068). CONCLUSIONS: Peer intervention improved the HRQoL of people recently diagnosed with HIV, and enhanced psychological health and social relationships covariate with their immunological recovery. This study represents an essential advance in evaluating peer intervention programmes for positive prevention.

New diketopiperazines as vectors for peptide protection and brain delivery: Synthesis and biological evaluation.

New strategies allowing the transfer of molecules, especially peptides, through the blood-brain barriers are a major pharmacological challenge for the treatment of brain diseases. The present study aims at evaluating in vivo the cerebral bioavailability of carrier systems, based on small and functionalizable 2,5-diketopiperazine (DKP) motifs. We studied 2 different cyclo(Lys-Lys) DKP scaffolds alone and a cyclo(Lys-Gly) DKP carrier bearing as peptide model, the tau protein hexapeptide VQIVYK sequence. The different carrier systems were synthesized and radiolabeled using one of the free domains. The stability, biodistribution, and ability to cross blood-brain barrier were investigated in vivo in mice for 99m Tc-DKP scaffolds, 99m Tc-HVQIVYK peptide alone, and 99m Tc-DKP-VQIVYK. 125 I-labelled bovine serum albumin was used as negative control for brain uptake. Both radiolabeled DKPs scaffolds and 99m Tc-DKP-VQIVYK showed a high stability, while peptide 99m Tc-HVQIVYK alone was quickly degraded in vivo. The presence of 99m Tc-DKPs scaffolds and 99m Tc-DKP-VQIVYK was observed in the ventricular and subarachnoid spaces and to a lower extent in the brain parenchyma up to 45 minutes post-injection in mice. This work highlights the potentiality of DKP scaffolds as vectors to transport peptides into the brain by limiting proteolysis and favoring cerebral bioavailability.

Enclavado retrógrado en fractura tibial / Retrograde nailing in a tibial fracture

Se describe un caso de fractura abierta de tibia grado iiia con gran conminución y pérdida distal de stock óseo ( cm) con total afectación de la superficie articular tibial y gran inestabilidad de la articulación peroneo-astragalina. El tratamiento realizado consintió en practicar una exhaustiva limpieza, colocándose un enclavado fresado retrógrado calcáneo-astrágalo-tibial con bloqueos proximales y distales, además de una aguja de Kirschner peroneo-astragalina. Se consiguió el cierre primario de la piel. A las 3 semanas se procedió al aporte de injerto óseo autólogo de cresta ilíaca rellenando el defecto óseo, a la reimpactación del clavo endomedular que estaba protuido distalmente y a la dinamización distal. Se consiguió la consolidación del defecto óseo en 16 semanas. Actualmente, el paciente deambula sin dolor con la artrodesis tibio-astragalina consolidada (AU)

We describe a case of a severely comminuted type iiia open tibial fracture, with distal loss of bone stock (7 cm), total involvement of the tibial joint surface, and severe instability of the fibular-talar joint. The treatment performed consisted of thorough cleansing, placing a retrograde reamed calcaneal-talar-tibial nail with proximal and distal blockage, as well as a fibular-talar Kirschner nail. Primary closure of the skin was achieved. After 3 weeks, an autologous iliac crest bone graft was performed to fill the bone defect, and the endomedullary nail, which had protruded distally was reimpacted and dynamized distally. The bone defect was eventually consolidated after 16 weeks. Currently, the patient can walk without pain the tibial-astragal arthrodesis is consolidated (AU)

[Retrograde nailing in a tibial fracture]. / Enclavado retrógrado en fractura tibial.

We describe a case of a severely comminuted type iiia open tibial fracture, with distal loss of bone stock (7 cm), total involvement of the tibial joint surface, and severe instability of the fibular-talar joint. The treatment performed consisted of thorough cleansing, placing a retrograde reamed calcaneal-talar-tibial nail with proximal and distal blockage, as well as a fibular-talar Kirschner nail. Primary closure of the skin was achieved. After 3 weeks, an autologous iliac crest bone graft was performed to fill the bone defect, and the endomedullary nail, which had protruded distally was reimpacted and dynamized distally. The bone defect was eventually consolidated after 16 weeks. Currently, the patient can walk without pain the tibial-astragal arthrodesis is consolidated.

Fracturas abiertas / Open fractures

Se presenta una revisión del estado actual del tratamiento de las fracturas abiertas. Procurando despejar controversias y establecer los principios básicos de su tratamiento actual. El empleo de antibióticos en el tratamiento inicial de las fracturas abiertas es un concepto bien establecido, cuanto más precoz es su administración mayor es la reducción de la posibilidad de infección. Cuanto más radical es el desbridamiento, menor es la tasa de infección. El método de fijación de elección para las fracturas abiertas de las diáfisis de la extremidad inferior es el enclavado endomedular. El uso de fijadores externos debería limitarse a los casos de politraumatismos. Si el desbridamiento ha sido exhaustivo, se obtiene un mejor resultado con el cierre primario de la herida. Se debe reparar la pérdida de partes blandas tan pronto como sea posible y mediante el uso del sistema más simple pero eficaz en la escalera ortoplástica: cierre secundario, injerto libre, colgajo rotacional, colgajo libre microvascularizado. Aunque algunas pautas de tratamiento son claras, cada fractura abierta es distinta por lo cual el tratamiento debe ajustarse a cada fractura y a cada paciente (AU)

A review is presented on the current status of open fracture treatments, and an attempt is made to clear up controversies and establish the basic principles of their current treatment. The use of antibiotics in the initial treatment of open fractures is a well known concept, and the earlier they are given the greater is the reduction in the likelihood of infection. The more radical the debridement is, the lower the rate of infection. The fixation method of choice for open fractures of the diaphysis of the leg is the intramedullary nail. The use of external fixation should be limited to cases of multiple traumas. If the debridement has been exhaustive, a better result is obtained with the primary closure of the wound. The loss of soft tissue must be repaired as soon as possible and using the simplest but most efficient system on the orthoplastic ladder; secondary closure, free graft, rotational flap, free microvascularised flap. Although some treatment guidelines are clear, each open fracture is different and must be adapted to each fracture and to each patient (AU)

[Viral biosafety, biosecurity, and bioterrorism]. / Biosécurité, biosureté et bioterrorisme viral.

Intentional release of infectious agents has always been considered as a possible weapon. Today this risk has expanded from use for wartime mass destruction to small-scale terrorist acts. Viruses, some of tropical origin, constitute a special biological hazard for several reasons: great infectious potential, adaptability to the host, difficulty for diagnosis in the hospital, and absence of specific treatment for the main agents involved. Handling of the dangerous biological agents requires special biocontainment laboratories equipped and classified according to increasing risk up to level 4. This article discusses the modalities of classification.

Standardization of needlestick injury and evaluation of a novel virus-inhibiting protective glove.

Rubber surgical gloves worn as a barrier to prevent contamination from body fluids offer relative protection against contamination through direct percutaneous injuries involving needles, scalpel blades or bone fragments. To determine the main experimental parameters influencing the volume of blood transmitted by a hollow-bore needle (worst case scenario) during an accidental puncture, we designed an automatic puncture apparatus. Herpes simplex type 1 virus (HSV1), a model for enveloped viruses, was used as a 'marker' in an in-vitro gelatine model. Of the experimental parameters studied, the most critical influences were found to be needle diameter and puncture depth, whereas puncture speed, puncture angle and glove-stretching feature appeared to be less influential. A single glove reduced the volume of blood transferred by 52% compared with no glove, but double gloving offered no additional protection against hollow-bore needle punctures. Using 'standardized' puncture conditions, the virus-inhibiting surgical glove G-VIR elicited an 81% reduction in the amount of HSV1 transmitted as compared with single or double latex glove systems.

Suitability of electronic mini-boluses for early identification of lambs.

Three types of ceramic mini-boluses, B1 [13.8 g; 10.5 x 51.0 mm (o.d. x length)], B2 (16.2 g; 12.2 x 42.2 mm), and B3 (20.1 g; 11.2 x 56.4 mm), were used to electronically identify as soon as possible after birth a total of 545 lambs of 3 breeds: Ripollesa (meat breed, n = 274), Manchega (dairy breed, n = 129), and Lacaune (dairy breed, n = 142). Boluses were administered by a trained operator using a balling gun or directly by hand. Lambs were also identified with 2 types of plastic ear tags in the left (temporary, 1.5 g) and the right (permanent, 4.1 g) ears. Lamb and identification device performances were checked during suckling (to wk 5 or 7) and fattening. At 24 kg of BW, lambs were slaughtered (n = 385) or kept for breeding (n = 144). No differences in performance were observed between the 2 dairy breeds, and their data were pooled. Minimum BW for bolus administration was lower in dairy than in meat lambs (P < 0.001). Across breeds, B1 and B3 did not differ in lamb age (27 d) and weight (9.2 kg) at administration, but B2 required older and heavier lambs (33 d and 11.1 kg; P < 0.01). Boluses did not affect lamb performance, but final readability at slaughter differed between B1 and B2 (97.7 and 95.2%, respectively) and B3 (100%), and between ear tags (temporary, 98.1; permanent, 100%). Bolus recovery was 100% in all cases, but the proportion of boluses found in the reticulum varied among bolus type (83.3 to 93.8%; P < 0.05). Three B1 (2%) were recovered from the abomasum. In a second experiment, effects of the intermediate mini-bolus (B2) on diet digestibility were evaluated. Digestibility of control and bolus-administered, Manchega ram lambs (14.9 kg of BW; n = 8) fed ad libitum with 2 pelleted concentrates and barley straw was assessed in digestibility crates. Feed intake and nutrient digestibility were measured in four 21-d periods, during which lambs received the 2 diets consecutively. No differences in intake, growth performance, or nutrient digestibility were observed between control and bolused lambs. In conclusion, the B3 mini-bolus proved to be an efficient device for identification of lambs before weaning (recommended age, >4 wk; recommended BW, >10 kg), allowing a reliable traceability of dairy and meat lambs until slaughter.

Bioterrorism: management of major biological agents.

Bioterrorism is defined by the intentional or threatened of microorganisms or toxins derived from living organisms to cause death or diseases in humans, animals or plants on which we depend. The other major point is to generate fear in the population. More than 180 pathogens have been reported to be potential agents for bioterrorism. The following is an overview of several agents that could be involved in a biological attack.

Retention of different sizes of electronic identification boluses in the forestomachs of sheep.

Twelve types of electronic identification ruminal boluses of different dimensions were used to obtain a model for predicting their retention in the forestomachs of sheep. Boluses (n = 1,662) were made of ceramic materials, and their dimensions varied in o.d. (9 to 21 mm), length (37 to 68 mm), volume (2.5 to 21.0 mL), and specific gravity (0.85 to 3.91). Each bolus contained a half-duplex, standardized, glass-encapsulated transponder (32 x 3.8 mm). Boluses were administered to sheep (n = 1,497) of different ages by using the appropriate balling guns, and their retention under semiintensive conditions was recorded for at least 2 yr. When a bolus was lost, the sheep was rebolused with a heavier bolus. All sheep wore 2 plastic ear tags: one for the official control of health programs and the other for farm use. To determine the anatomical limit for a bolus passing through the gastrointestinal tract, the size of the reticulo-omasal orifice was measured in 46 adult sheep (male, n = 14; female, n = 32) that died by causes not related to bolus administration during the experiment. No signs of disease or growth alteration were detected in the bolused sheep. Total ear tag losses during the experiment period were 7.5% on average. Bolus retention (5 to 100%) varied according to bolus features and age of the sheep, but it showed a plateau after 18 mo. Inadequately dimensioned boluses were regurgitated or passed through the gastrointestinal tract and were excreted with the feces. The diameter of the reticulo-omasal orifice in adult sheep differed between male and female (23.1 and 21.8 mm, respectively; P < 0.01) and was greater than the o.d. of the retained boluses. Retention rate was predicted from bolus weight and volume by a logistic regression (R2 = 0.997; P < 0.001). When retention data from the literature (59.0 to 100%) were included in the model, the adjustment was slightly lower (R2 = 0.967). As a result, the minimum bolus weight estimated to reach a 99.5% retention rate in sheep varied between 16 and 45 g when volume varied between 3 and 22 mL, for boluses with a specific gravity between 2.0 and 5.2. In conclusion, bolus retention rate in sheep varied dramatically according to their features. For safe and efficient retention of electronic identification boluses in sheep, boluses of small volume and diameter (e.g., < 15 mm) with specific gravity and weight greater than 3.0 and 20 g, respectively, are recommended.

Evaluation of the retention of electronic identification boluses in the forestomachs of cattle.

A total of 1,203 beef calves were used to evaluate 2 series of electronic identification boluses. Calves were intensively fattened and slaughtered at approximately 1 yr of age. Series 1 (n = 576 calves) consisted of 10 types of boluses with the same external dimensions (o.d. x length: 21 x 68 mm) but varying in weight (11 to 75 g) and specific gravity (0.63 to 3.36). Six boluses were made of ceramic (5 prototypes and 1 commercial bolus) and 4 were tubes made of plastic filled with concrete. Series 2 (n = 627 calves) consisted of 3 prototypes and 5 commercial boluses of different ceramic materials varying in external dimensions (o.d.: 15 to 21 mm; length: 39 to 78 mm), weight (20 to 73 g), and specific gravity (3.00 to 3.87). Boluses were administered to milk-fed calves (2 to 5 wk of age) by using adapted balling guns. To determine the anatomical limit for a bolus passing through the gastrointestinal tract, the size of the reticuloomasal orifice was measured in 90 male and 62 female fattened calves at slaughter. Three calves in series 1 (0.3%) could not swallow the 21-mm (o.d.) bolus at the first attempt and received the bolus 1 wk later. No problems for early administration were found with thinner boluses (o.d. < 20 mm) in series 2, and no signs of disease or growth alteration were detected in any bolused calves. Retention rate until slaughter varied according to bolus features and ranged from 0 to 100% (series 1), and from 69.7 to 100% (series 2). Inadequately dimensioned boluses were regurgitated or passed through the gastrointestinal tract and were excreted with the feces. The diameter of the reticuloomasal orifice differed between male and female yearling calves (32.5 and 29.9 mm, respectively; P < 0.01) and was greater than the o.d. of the retained boluses. Retention rate was predicted from bolus weight and volume by a logistic regression (R2 = 0.99, P < 0.001), in which the minimum bolus weight estimated to reach a 99.5% retention rate was 61 g when volume and specific gravity were 22.4 mL and 2.72, respectively. To achieve an effective retention rate of electronic identification boluses in the forestomachs of fattening calves, bolus volume and specific gravity, in addition to weight, should be optimized. No boluses of specific gravity lower than 3.0 and thicker than 20 mm o.d. are recommended for identification of cattle from early rearing (< 20 d of age) to slaughtering.

Evaluation of a Crimean-Congo hemorrhagic fever virus recombinant antigen expressed by Semliki Forest suicide virus for IgM and IgG antibody detection in human and animal sera collected in Iran.

Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by ticks or by direct contact with infected blood. It causes severe, often fatal, hemorrhagic diseases in humans but infection in animals is asymptomatic. CCHFV can spread from person to person and has caused many nosocomial outbreaks. Because the virus is very pathogenic for humans it must be manipulated in a biosafety level 4 (BSL4) laboratory, rendering the production of antigen for serological diagnosis difficult. To replace the native antigen, we produced a recombinant nucleoprotein expressed in mammalian cells via the recombinant Semliki Forest alphavirus replicon and developed an indirect immunofluorescence assay (IFA) as well as an enzyme-linked immunosorbent assay (ELISA) by immunocapture to detect IgM and IgG in human and animal serum. Using these methods, we analyzed clinical samples from human patients and sera from domestic animals collected in Iran and we show that this novel antigen provides a novel, sensitive and specific tool for CCHF diagnosis.

Use of ear tags and injectable transponders for the identification and traceability of pigs from birth to the end of the slaughter line.

A total of 557 newborn piglets were used to compare eight identification devices, including one plastic ear tag as a control (C, n = 348) and two types of electronic ear tags (E1, n = 106; and E2, n = 103), and five types of injectable transponders (n = 557): small 12-mm (D12, n = 116; and S12, n = 110), medium 23-mm (T23, n = 108), and large (32-mm, T32, n = 115; and 34-mm, S34, n = 108). Injections were made s.c. in the auricle base (n = 248) and intraperitoneally (n = 309) using a new technique. All piglets were identified with two devices, but using electronic ear tags in conjunction with injection in the auricle was avoided on the same pig. Readability of devices was checked during fattening (until 110 kg BW) and slaughtering. On-farm losses were lower for control than for electronic ear tags (C = 1.1%; E1 = 8.8%; and E2 = 44.9%; P < 0.01); the latter also suffered electronic failures (E1 = 5.5%; and E2 = 55.1%; P < 0.001). On-farm losses of transponders injected in the auricle base were greater in large (S34 = 72.5%; and T32 = 46.3%; P < 0.05) than in small transponders (S12 = 19.4%; and D12 = 17.1%), but T23 (29.8%) only differed from S34. Transponder size did not affect on-farm losses for intraperitoneal injections in which only one loss was recorded (0.4%). All ear tags had similar losses during transportation to the slaughterhouse (1.2%), but no losses were observed in injectables. Slaughtering losses did not differ between ear tags (C = 11.2%; and E1 = 6.4%), but apart from losses, 12.8% of E1 failed electronically. Injection site affected losses and breakages during slaughtering (auricle base = 6.4%; and intraperitoneal = 0%), but recovery time did not significantly differ (auricle base = 28.6 s; and intraperitoneal = 18.9 s). Transponders in the auricle base were recovered by sight (30.2%), palpation (27.4%), or by cutting (42.5%). Intraperitoneal transponders were mainly recovered loose in the abdominal cavity (81.4%), whereas 18.6% fell on the floor. As a result, traceability varied significantly (P < 0.05) between control (86.7%) and electronic ear tags (0 to 68.1%) and injectable transponders, with the auricle base (17.8 to 75.0%) having lower values than intraperitoneal (98 to 100%). Intraperitoneal injection was a very effective tool for piglet identification and traceability, ensuring the transfer of information from farm to slaughterhouse. To warrant the use of this technique in practice, transponder recovery requires further investigation.

Nonhuman primates are relevant models for research in hematology, immunology and virology.

Nonhuman primates have been used for biomedical research for several decades. They have proved to be models that are relevant to humans because of the high level of gene homology which underlies physiological and biochemical similarities. The similarity of monkeys to humans has been used to investigate pathophysiological mechanisms in hematology, immunology and virology. New therapeutic procedures can be assessed in primates by using materials, in particular pharmacological reagents, and methods designed for humans. The relevance of these models also relies on the use of species-specific pathogens and the availability of recombinant, homologous cytokines. The introduction of more and more sophisticated cell and gene therapy protocols in hematopoietic cell transplantation and immunotherapy requires the development of preclinical trials similar to clinical settings. For several decades now, baboons and cynomolgus/rhesus monkeys have been the most useful primate models in experimental hematology, and this has contributed to numerous therapeutic advances. Primate models of AIDS have been developed to study the pathogenesis, transmission and immune responses to infection, and to test vaccines and drugs. Primate research should be restricted in quantity, and mainly designed with the aim of removing uncertainty as to the safety and clinical benefit to the patient, of new biomedical protocols.

[Risk of smallpox, vaccination, bioterrorism]. / Risque de variole, vaccination et bioterrorisme.

The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.

[Update on smallpox vaccines]. / Actualités sur la vaccination antivariolique.

Smallpox is among the most dangerous pathogens that could be used by bioterrorists. The former vaccines produced by scarification on the flanks of calves or sheep could be used to protect the whole French population when used with bifurcated needles. They should be replaced by a second-generation vaccine grown in cell culture and, eventually later by new and safer third-generation vaccines using non-replicative viral strains.

Rapid inactivation of vaccinia virus in suspension and dried on surfaces.

A bioterrorist attack with smallpox virus would be disastrous with a 30% disease fatality rate. Such an outbreak would require biomedical laboratories for diagnosis and analyses and extensive use of clinical care facilities for patient quarantine. Safe decontamination procedures will have to be in place in order to limit the spread of the disease. In order to fulfil this need, Sanytex, a new non-corrosive commercial solution containing quaternary ammonium, aldehydes, alcohol and detergent, was tested with a view to using it in decontamination procedures. Vaccinia virus was used in this investigation as a model for smallpox virus. We determined exposure time and the concentration of Sanytex required to inactivate the virus in suspension and dried on surfaces in the presence of protein (up to 70 mg/mL). After 3 min incubation, Sanytex at a concentration of 3% led to a complete inactivation (virus titre reduction >10(4)-fold of vaccinia virus in suspension containing protein up to 30 mg/mL. A virus suspension containing 70 mg protein/mL, simulating biological fluids, was decontaminated with 10% Sanytex after 3 min. After 10 min, Sanytex at a concentration of 30%, applied on to a dried vaccinia virus contaminated surface in the presence of protein (10 mg/mL before desiccation), led to complete decontamination of the surface. Thirty minutes exposure with 30% Sanytex was necessary for a virus titre reduction of >10(4)-fold on a surface contaminated with a dried suspension of vaccinia virus in the presence of protein at 70 mg/mL. Sanytex is not corrosive, not toxic to environment and stable for up to three months even diluted. Its virucidal effect was preserved when used under pressure in a fire-hose nozzle. These results support the use of Sanytex for decontamination of biological fluids and surfaces contaminated by the smallpox virus.

In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination.

Chikungunya virus (CHIKV) and Semliki Forest virus (SFV) were used in our laboratory to screen active antiviral compounds against viruses of the Alphavirus genus. Antiviral activity was estimated by the reduction of the cytopathic effect of each alphavirus on infected Vero cells and by virus titer reduction. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion in confluent cell cultures and by the evaluation of the inhibitory effect on cell growth. With CHIKV and SFV, the selectivity indices of human recombinant interferon-alpha and iota-carrageenan were much higher than that of ribavirin, which has been previously investigated for its inhibitory effect on alphavirus infections. Compared to ribavirin, 6-azauridine was more effective against CHIKV and showed a similar antiviral activity against SFV. IFN-alpha2b, glycyrrhizin, 6-azauridine, and ribavirin caused a concentration-dependent reduction in the virus yield with CHIKV and SFV. Moreover, the combination of IFN-alpha2b and ribavirin had a subsynergistic antiviral effect on these two alphaviruses and should be evaluated for the treatment of these infections.