Treatment Of Established Infection Research Articles

Nephrotoxicity of Amoxicillin and Third-Generation Cephalosporins: An Updated Review.

Because of their broad-spectrum bactericidal activity, amoxicillin (AMX) and third-generation cephalosporins (TGC) are widely used for the prophylaxis and treatment of established infections. They are considered relatively safe, but several recent reports have suggested substantial nephrotoxicity, especially with AMX use. Considering the importance of AMX and TGC for clinical practice, we conducted this up-to-date review, using the PubMed database, which focuses specifically on the nephrotoxicity of these molecules. We also briefly review the pharmacology of AMX and TGC. Nephrotoxicity of AMX may be driven by several pathophysiological mechanisms, such as a type IV hypersensitivity reaction, anaphylaxis, or intratubular and/or urinary tract drug precipitation. In this review, we focused on the two main renal adverse effects of AMX, namely acute interstitial nephritis and crystal nephropathy. We summarize the current knowledge in terms of incidence, pathogenesis, factors, clinical features, and diagnosis. The purpose of this review is also to underline the probable underestimation of AMX nephrotoxicity and to educate clinicians about the recent increased incidence and severe renal prognosis associated with crystal nephropathy. We also suggest some key elements on the management of these complications to avoid inappropriate use and to limit the risk of nephrotoxicity. While renal injury appears to be rarer with TGC, several patterns of nephrotoxicity have been reported in the literature, such as nephrolithiasis, immune-mediated hemolytic anemia, or acute interstitial nephropathy, which we detail in the second part of this review.

Microbial Interspecies Associations in Fracture-Related Infection.

Describe co-occurrence or clustering of microbial taxa in fracture-related infections to inform further exploration of infection-related interactions among them. Retrospective review. Level 1 trauma center. Four hundred twenty-three patients requiring surgical intervention for deep surgical site infection between January 2006 and December 2015. None. Connection between microbial taxa. Methicillin-resistant Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, and coagulase-negative Staphylococcus represented the majority of monomicrobial observations (71%). Gram-negative rods, gram-positive rods, and anaerobes presented more frequently in polymicrobial infections. Enterobacter, vancomycin-sensitive Enterococcus, and Pseudomonas are present in polymicrobial infections with the highest frequencies and represent the top 3 most important nodes within the microorganism framework, with the highest network centrality scores. The present study indicates that there are common microbial taxa (Enterobacter, Enterococcus, and Pseudomonas) that tend to co-occur with other microbes greater than 75% of the time. These commonly co-occurring microbes have demonstrated interactive relationships in other disease pathologies, suggesting that there may be similar important interactions in fracture-related infections. It is possible that these microbial communities play a role in the persistently high failure rate associated with management of infection after trauma. Future studies are needed to study the intermicrobial interactions that explain the frequency at which taxa co-occur. Understanding and potentially disrupting these intermicrobial relationships could inform improvements in the treatment of established infections and in the prevention of infection in high-risk patients. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Approaches to Integrated Parasite Management (IPM) for Theileria orientalis with an Emphasis on Immunity.

Integrated parasite management (IPM) for pests, pathogens and parasites involves reducing or breaking transmission to reduce the impact of infection or infestation. For Theileria orientalis, the critical impact of infection is the first wave of parasitaemia from the virulent genotypes, Ikeda and Chitose, associated with the sequelae from the development of anaemia. Therefore, current control measures for T. orientalis advocate excluding the movement of naïve stock from non-endemic regions into infected areas and controlling the tick Haemaphysalis longicornis, the final host. In Australia, treatment of established infection is limited to supportive therapy. To update and expand these options, this review examines progress towards prevention and therapy for T. orientalis, which are key elements for inclusion in IPM measures to control this parasite.

Generation of a cost-effective cell line for support of high-throughput isolation of primary human B cells and monoclonal neutralizing antibodies

The isolation of human monoclonal antibodies (mAbs) arising from natural infection with human pathogens has proven to be a powerful technology, facilitating the understanding of the host response to infection at a molecular level. mAbs can reveal sites of vulnerability on pathogens and illuminate the biological function of the antigenic targets. Moreover, mAbs have the potential to be used directly for therapeutic applications such as passive delivery to prevent infection in susceptible target populations, and as treatment of established infection. The isolation of antigen-specific B cells from vaccine trials can also assist in deciphering whether the desired B cells are being targeted by a given vaccine. Several different processes have been developed to isolate mAbs, but all are generally labor-intensive and result in varying degrees of efficiency. Here, we describe the development of a cost-effective feeder cell line that stably expresses CD40-ligand, interleukin-2 and interleukin-21. Sorting of single B cells onto a layer of irradiated feeder cells sustained antibody production that permits functional screening of secreted antibodies in a manner that enables subsequent recovery of B cells for recombinant antibody cloning. As a proof of concept, we show that this approach can be used to isolate B cells that secrete antibodies that neutralize human papilloma virus (HPV) from participants of an HPV vaccine study.

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection.

Infection by Leishmania (Viannia) panamensis, the predominant etiologic agent for cutaneous leishmaniasis in Colombia, is characterized by a chronic mixed inflammatory response. Current treatment options are plagued by toxicity, lengthy treatment regimens, and growing evidence of drug resistance. Immunotherapy, modulating the immune system to mount a protective response, may provide an alternate therapeutic approach. We investigated the ability of the Toll-like receptor 9 (TLR9) ligand CpG to modulate established disease in the L (V) panamensis mouse model. Treatment of established infection with a high dose (50 μg) of CpG ameliorated disease and lowered parasite burden. Interestingly, immediately after treatment there was a significant increase in transforming growth factor β (TGF-β) and concomitantly an increase in T regulatory cell (Treg) function. Although a general reduction in cell-mediated immune cytokine and chemokine (gamma interferon [IFN-γ], interleukin 10 [IL-10], IL-13, IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-4, and MIP-1α) responses of the treated mice was observed, certain chemokines (RANTES, monocyte chemoattractant protein 1[MCP-1], and IP-10) were increased. Further, in peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis, CpG treatment similarly exhibited a dose-response effect on the production of IFN-γ, IL-17, IL-10, and IL-13, with reductions observed at higher doses. To further understand the underlying mechanisms and cell populations driving the CpG mediated response, we examined the ex vivo dose effects mediated by the TLR9+ cell populations (dendritic cells, macrophages, and B cells) found to accumulate labeled CpG in vivo Notably, B cells altered the production of IL-17, IL-13, and IFN-γ, supporting a role for B cells functioning as antigen-presenting cells (APCs) and/or regulatory cells during infection. Interestingly, B cells have been previously demonstrated as a primary type of APC in patients infected with L (V) panamensis and thus may be useful targets of immunotherapy. Collectively, our results show that CpG-induced immune regulation leads to a dampening of the host immune response and healing in the mouse model, and it may provide an alternate approach to treatment of cutaneous leishmaniasis caused by L (V) panamensis.

HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7

The cervical cancer is one of the most common diseases in world. This malignancy is the seventh highest prevalence oncological disease worldwide and the second highest prevalence oncological disease of women in the world. Meanwhile women need to be infected by human papilloma virus (HPV) is absolutely necessary for it further evolution, HPV DNA was found in 99.97% cases of disease. Except cervical cancer, HPV cause 85% of rectal cancer, 50% of the vulva, vagina and penis cancers, 20% of oropharyngeal cancer and 10% of larynx and esophagus cancers. In 2009, 14 000 women were diagnosed with cervical cancer in Russia. The growth in morbidity was 19% (in comparison with 1999). The most effective recognised measure for almost each infection prophylaxis is a vaccination. Two human papilloma virus vaccines are available in Russia nowadays Gardasil and Cervarix, produced in Belgium and the Netherlands respectively. Cervarix is a bivalent vaccine based on virus-like particles (VLP) of two types. Recombinant major capsid proteins L1 HPV 16 and HPV 18 express in baculovirus expression system and self-assembled into virus-like particles (about 70 percent of cervical cancers are caused by HPV 16 and HPV 18). VLP of each strain produced in different baculovirus vectors and then combined in single drug. Gardasil is like Cervarix with few exceptions. Producing organisms are fungi S. cerevisiae in this case, and this vaccine contains low-risk HPV 6 and HPV 11 VLP. Thus, Gardasil is quadrivalent HPV-6/11/16/18 vaccine. These vaccines are very effective in averting infection of disease and dont have significant side-effects, however they have some disadvantages. Firstly, they have a high price because of necessity of their expression in eukaryotic cells. Secondly, they are strain-specific, so vaccines are completely effective only for viruss strains which are represented in the vaccine. Thirdly, it`s the absence of therapeutic (treatment of established infection) value of stated vaccines. According to information from literature, N-terminus of the L2 protein can induce non strain-specific neutralizing antibody that protects organism from papillomavirus challenge. E7 protein is a virus oncogene, its function is unlimited proliferation of infected cells that cause malignization in chronic course of disease. This protein is a very attractive target for therapeutic vaccines because of its necessity both for virus life cycle and sustenance of malignant phenotype in cancer cells. So, in this research the design of immunogen on the base of proteins HPV L2 and E7 is selected, vaccine on the base of which will avoid the disadvantages of Gardasil and Cervarix listed above. The stain-producer of protein on the base of cells E. coli was created. The protein was purified in denaturing reducing conditions by metal-affine chromatography and refold by sequential remove of urea and 2-mercaptoethanol.

Infection After Orthopaedic Trauma: Prevention and Treatment

Trauma to the extremities is disproportionately represented in casualties of recent conflicts, accounting for >50% of injuries sustained during operations in Iraq and Afghanistan. Infectious complications have been reported in >25% of those evacuated for trauma, and 50% of such patients were treated in the intensive care unit (ICU). Osteomyelitis has been reported in 9% (14% of intensive care unit patients), and deep-wound infection in 27% of type III open-tibia fractures. Infections complicating extremity trauma are frequently caused by multidrug-resistant bacteria and have been demonstrated to lead to failure of limb salvage, unplanned operative take-backs, late amputations, and decreased likelihood of returning to duty. Invasive fungal infections of extremities have also presented a unique challenge in combat-injured patients, particularly in those with blast injuries with massive transfusion requirements and high injury severity scores. Infection prevention should begin at the time of injury and, although context-specific depending on the level of care, includes appropriate irrigation, surgical debridement, wound care and coverage, fracture fixation, and antibiotic prophylaxis, in addition to basic infection prevention measures. Clinical practice guidelines to address infection prevention after combat trauma (including extremity infection) were developed in 2007 and revised in 2011, with endorsement from the Surgical Infection Society and the Infectious Disease Society of America. Nevertheless, significant challenges remain, including austere environments of care, multiple transitions of care, and lack of coordinated efforts in prevention. Treatment of established infections is optimally multidisciplinary, particularly when deep wounds, bone, and joints are involved. Surgical debridement of overtly infected or necrotic tissue is necessary, with particularly aggressive margins if invasive fungal infection is suspected. Infected nonunion frequently requires the use of prosthetic materials for fixation, potentiating biofilm formation, and complicating medical therapy. Antibiotic therapy should be targeted at results of deep wound and bone cultures. However, this is complicated by frequent contamination of wounds, requiring differentiation between potential pathogens in terms of their virulence and decreased culture recovery in patient who have frequently received previous antibiotics. Lessons learned in infection prevention and treatment of orthopaedic trauma from combat can serve to inform the care of patients injured in natural disasters and noncombat trauma.

Knowledge, Attitude and Practice towards PMTCT of HIV among Women Attending Ambo Hospital ANC Clinic, West Ethiopia

Background: Every day there are nearly 1800 new HIV infections in children under 15 years of age, more than 90% occurring in the developing world. Most (about 90%) of these infections are associated with mother-to-childtransmission (MTCT). Moreover about, 1400 children under 15 years of age die of an HIV-related illness per day. Hence, this study tried to assess the knowledge, attitude, and practice with prevention of mother-to-child transmission of HIV/AIDS among pregnant mothers attending antenatal clinic. Methods: An institution-based cross-sectional study was conducted among pregnant mothers attending antenatal care clinic at Ambo General Hospital from April 1-May 30, 2014. A systematic random sampling technique was used to select 238 antenatal care attendees. Data were collected through structured pre-tested questionnaire. The data were entered into Epi Info and analyzed by using SPSS software for windows. Frequency and percentage were done. Results: The study showed that all of the respondents heard about HIV/AIDS and about MTCT of HIV. Concerning the time of transmission of the virus from the infected mother to her child, 74 (31.4%) responded that it could be through breast feeding, 69 (29.2%) during pregnancy, 6 (27.5%) during labor and 2 (11.9%) did not know respectively. All the respondents have been tested for HIV. Among these, 87 (36.38%) tested six months ago, 76 (32.2%) tested three months ago, 37 (15.7%) tested one year ago and 36 (15.3%) tested on the recent pregnancy. All of them had preand post-counseling services. The study have showed that most of the respondents, 221 (93.6%), had good attitude towards PMTCT of HIV, while only 6.4 (28.73%) had poor attitude. Conclusion: Accordingly all of the mothers knew about prevention of mother-to-child transmission of HIV and 93.6% had good attitude towards it. Only 44.4% of the respondents knew that antiretroviral drugs given for seropositive pregnant mothers could reduce the risk of HIV transmission. All the of mothers have been tested for HIV/ AIDS. Much has better to be done to maintain mothers knowledge, attitude and of all to promote the use of ART and other PMTCT of HIV methods through organized intervention programs as well as by ensuring the supply of the ART medications used for PMTCT of HIV beside the treatment of established infection.

Preferential Lymphatic Growth in Bronchus-Associated Lymphoid Tissue in Sustained Lung Inflammation

Lymphatics proliferate, become enlarged, or regress in multiple inflammatory lung diseases in humans. Lymphatic growth and remodeling is known to occur in the mouse trachea in sustained inflammation, but whether intrapulmonary lymphatics exhibit similar plasticity is unknown. We examined the time course, distribution, and dependence on vascular endothelial growth factor receptor (VEGFR)-2/VEGFR-3 signaling of lung lymphatics in sustained inflammation. Lymphatics in mouse lungs were examined under baseline conditions and 3 to 28 days after Mycoplasma pulmonis infection, using prospero heomeobox 1-enhanced green fluorescence protein and VEGFR-3 as markers. Sprouting lymphangiogenesis was evident at 7 days. Lymphatic growth was restricted to regions of bronchus-associated lymphoid tissue (BALT), where VEGF-C-producing cells were scattered in T-cell zones. Expansion of lung lymphatics after infection was reduced 68% by blocking VEGFR-2, 83% by blocking VEGFR-3, and 99% by blocking both receptors. Inhibition of VEGFR-2/VEGFR-3 did not prevent the formation of BALT. Treatment of established infection with oxytetracycline caused BALT, but not the lymphatics, to regress. We conclude that robust lymphangiogenesis occurs in mouse lungs after M. pulmonis infection through a mechanism involving signaling of both VEGFR-2 and VEGFR-3. Expansion of the lymphatic network is restricted to regions of BALT, but lymphatics do not regress when BALT regresses after antibiotic treatment. The lung lymphatic network can thus expand in sustained inflammation, but the expansion is not as reversible as the accompanying inflammation.

Antitrichomonal activity of 1-[(2,4-dnitropyrryl)-ethyl]-2methyl-5-nitroimidazole and related compounds.

Abstract A series of 1-substituted dinitropyrroles was tested for trichomonacidal activity. The shorter the substituent the greater was the in vitro activity. No relationship was found between in vivo activity and substituent length. A comparison of the trichomonacidal activities of 1-[(2,4-dinitropyrryl)-ethyl]-2-methyl-5-nitroimidazole (ORF-2245) and 1-(2-hydroxymethyl)-2-methyl-5-nitroimidazole (8823 R.P.) was made. ORF-2245 exhibited activity equal to or greater than 8823 R.P. except in the treatment of established infections where its limited activity was attributed to poor absorption from the gut. Absorption, however, was apparently sufficient to combat or prevent the low-grade infections.

Salvage of infected tumor prostheses

Limb salvage in oncologic surgery with endoprosthetic reconstruction results in infection in 5.7–15% of patients. These infections result in subsequent amputation in 46–87% of patients. Through literature review, we evaluated the statistically associated factors, treatments, outcomes and future trends regarding endoprosthetic infection. Infection was more prevalent in periacetabular and proximal tibial reconstructions. Coagulase-negative Staphylococcus was the most common pathogen in seven of eight case series. Factors associated with increased initial and persistent infection included myeloma, radiation therapy, poor soft-tissue condition, revision surgeries, and cementless fixation. Infection was noted to significantly increase 10-year survival in osteosarcoma patients. Recommendations on treatment were mixed, the only significant association with cure was early surgical intervention, and increased salvage rates were seen with both limited one-stage and extensive two-stage procedures. All studies agreed that clinicians and researchers should direct intensive efforts toward the prevention of infection. A number of recent studies showed promising in vitro and in vivo effects of antimicrobial implant surfaces, specifically silver and vancomycin, in retarding the establishment of periprosthetic infection. Infections of oncologic endoprostheses remain challenging problems, with no recent advances in the treatment of established infections. Associated factors have been established, although most are unavoidable in the course of cancer treatment. Most promise comes with the ongoing development of antimicrobial implant surfaces that aim to prevent the establishment and persistence of these difficult infections.

Trypanosomiasis: African and American

Abstract Human African trypanosomiasis has increased in many endemic areas in recent years. It is caused by Trypanosoma brucei gambiense or T. b. rhodesiense, and is transmitted by the tsetse fly. Diagnosis is difficult, particularly in the West African type, in which organisms are scanty. Determination of the stage of infection (early haemolymphatic stage or late meningoencephalitic stage) is also problematic, and the few drugs available are associated with significant toxicity. Advances in understanding of the cellular and molecular biology of the parasites causing African trypanosomiasis now must be matched with improvements in diagnosis and treatment of this condition, which has a current prevalence of about 300,000 cases. Chagas disease is caused by infection with T. cruzi carried by blood-sucking triatomine bugs. The infection is often latent for several years, before progressing in 15–30% of individuals to disabling organ involvement and ‘mega'-syndromes. This South American infection is difficult to diagnose and there is no effective treatment for established infection.

Use of Phage Display To Identify Potential Pseudomonas aeruginosa Gene Products Relevant to Early Cystic Fibrosis Airway Infections

Pseudomonas aeruginosa airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis. Treatment of established infections is difficult, even with microbiologically active agents. Thus, prevention of infection is an important goal of management. Isolates from cystic fibrosis patients appear to originate from the environment but adapt to the milieu of the airway of the cystic fibrosis patient and evolve toward a common phenotype. Identification of the antigens expressed early in infection may lead to novel targets for vaccine development. Immunogenic peptides were identified in a J404 random nonapeptide phage display library with serum from cystic fibrosis patients obtained within the first year of P. aeruginosa infection. One hundred sixty-five reactive clones were verified by plaque lift assays, and their inserts were sequenced. The sequenced nonapeptides were compared with the published sequence of strain PAO1, identifying homologies to 76 genes encoding outer membrane and secreted proteins. The majority of these were proteins involved in small-molecule transport, membrane structural proteins, and secreted factors. An in silico analysis was performed that suggested that the occurrence of multiple matches to predominantly outer membrane and secreted proteins was not attributable to random chance. Finally, gene expression array data from early isolates of P. aeruginosa from cystic fibrosis patients was compared with the results from phage display analysis. Eleven outer membrane and secreted proteins were common between the two data sets. These included genes involved in iron acquisition, antibiotic efflux, fimbrial biogenesis, and pyocin synthesis. These results demonstrate the feasibility and validity of this novel approach and suggest potential targets for future development.

The Role of Baseline HIV-1 Resistance Testing in Patients with Established Infection.

Effective long-term treatment of HIV-1 infection is challenging because of several factors, including antiretroviral drug resistance. Antiretroviral resistance testing has short-term benefit for optimizing the choice of a rescue regimen after treatment failure. Resistance testing also is recommended before therapy in pregnancy and acute infection or recent seroconversion. The benefit of routine resistance testing before starting treatment for established infection is less clear. This report summarizes the accumulating evidence of persistence of resistant mutants after initial infection, detectability of resistant virus with standard assays before treatment of established infection, the potential adverse impact of this baseline resistance on effectiveness of therapy, and the increasing prevalence of resistance in treatment-naïve patients. Taken together, these data suggest that pretreatment genotypic resistance testing also may be useful in patients with established infection. Although further study is needed, clinicians are now encouraged to routinely obtain pretreatment resistance testing.

Prophylaxis, empirical therapy, or pre-emptive therapy of fungal infections in immunocompromised patients: which is better for whom?

Immunocompromised patients are at risk of developing fungal infections. Over time, the incidence of fungal infections and the spectrum of causative organisms have changed. In addition, treatment strategies in this high-risk population have also changed. Traditional approaches (using polyene-based therapy and older azoles), including empirical treatment strategies, have evolved to include prophylaxis in populations at the greatest risk. These strategies, although effective against Candida species, have not really impacted infections caused by Aspergillus spp. With the recent approval of antifungal agents with demonstrated activity against Aspergillus and other mould infections, there is hope for better outcomes in the treatment of established infections. Several agents, with activity against Aspergillus, have been shown to be effective in the empirical setting. The role of these new antifungal agents in the prophylactic setting remains unknown at present, but the potential for reducing Aspergillus infections is promising and requires ongoing study. The other area of significant research in fungal infections has been the search for accurate, non-invasive, rapid diagnostic tests. Over the past year, several publications have indicated that early diagnosis is possible in immunocompromised patients. These new diagnostics have paved the way for a new strategy, called pre-emptive therapy, enabling infected patients to be identified at an earlier stage of infection. This strategy will permit targeted antifungal therapy in those at greatest risk, and will avoid unnecessary, potentially toxic therapy in those not infected. Validations of the various techniques show promise and are reviewed in this paper.

Antibody treatment of lower respiratory tract infections.

Antibody treatment of lower respiratory infection has a long history of success and is receiving renewed interest. A variety of polyclonal and monoclonal preparations are clinically available. Although used primarily for infection prophylaxis, these agents have limited applications in the treatment of established infections. Immune serum was the first effective treatment for pneumococcal pneumonia. Although long-supplanted by the advent of antibiotics, passive immunotherapy for pneumococcal and other infections is being revisited in an era of increasing antibiotic resistance and growing numbers of immunocompromised individuals. Limited clinical evidence supports the use of immune globulins in the treatment of pertussis and severe streptococcal infection. Bone marrow transplant recipients with lower respiratory infections caused by cytomegalovirus or respiratory syncytial virus also may benefit by adjunctive treatment with immune globulins. Additional indications for antibody treatment of respiratory infection may develop with further investigation.

Efficacy of an ivermectin controlled-release capsule against some rarer nematode parasites of sheep

A controlled trial was conducted to evaluate the efficacy of the intraruminal ivermectin controlled-release capsule (CRC) (IVOMEC ® Maximizer ™ CR Capsule for Sheep, Merial Ltd.) against induced incoming third-stage larvae and established adult infections with some rarer gastrointestinal nematode parasites of sheep. Twenty-one worm-free lambs were allocated by restricted randomisation based on body weight within sex to one of the following treatments: unmedicated control, ivermectin CRC given on Day 0 prior to induced infection, and ivermectin CRC given on Day 70 after establishment of induced infection. The ivermectin CRC delivers ivermectin at a minimum dose rate of 20 μg/kg/day for 100 days. Infections were induced by daily administration of third-stage larvae for five consecutive days. Nematodes were counted on Day 84, 14 days after treatment of established infection. The treatment with the ivermectin CRC prevented the establishment of Ostertagia leptospicularis, O. ostertagi, Bunostomum trigonocephalum, Cooperia oncophora, C. punctata, C. surnabada, Nematodirus helvetianus, N. roscidus and Strongyloides papillosus by >99% as compared with the untreated controls ( p < 0.01). The administration of the ivermectin CRC reduced established adult infections of O. ostertagi, B. trigonocephalum, C. oncophora, C. punctata, C. surnabada, N. roscidus and S. papillosus by >99% ( p < 0.01), and reduced established adult infections of O. leptospicularis and N. helvetianus by 96.5 and 98.4% ( p < 0.01), respectively.

Malnutrition, morbidity and mortality in children and their mothers.

While being underweight or stunted is recognized as an important risk factor for increased prevalence and severity of infection and high mortality rates, there is increasing evidence for an independent role for micronutrient deficiency. Improving vitamin A status reduces mortality among older infants and young children and reduces pregnancy-related mortality; it also reduces the prevalence of severe illness and clinic attendance among children. Improving Zn status reduces morbidity from diarrhoeal and respiratory infection. Treatment of established infection with vitamin A is effective in measles-associated complications, but is not as useful in the majority of diarrhoeal or respiratory syndromes. Zn supplements, however, have significant benefit on the clinical outcome of diarrhoeal and respiratory infections. Concerns that Fe supplements might increase morbidity if given in malarious populations appear to be decreasing, in the light of new studies on Fe supplements showing improved haemoglobin without an increase in morbidity. Breast-feeding, well known to protect against diarrhoea, is also important in protecting against respiratory infection, especially in the young infant. Transmission of human immunodeficiency virus (HIV) in breast milk is recognized, but new data showing reduced transmission in infants who receive exclusive breast-feeding rather than mixed feeding reinforces the importance of promoting this practice in areas where environmental contamination precludes the safe use of other infant feeding regimens. The presence of subclinical mastitis, now recognized to occur in approximately 20 % of mothers in several developing countries, has been shown to increase the concentration of HIV in breast milk. Preliminary findings suggest that the prevalence of subclinical mastitis is reduced by dietary supplements containing antioxidants. Governments and international agencies now have a strong scientific basis to be much more active and innovative in the introduction of focused nutrition interventions especially micronutrients, for the control of infection.

Keeping MRSA out of a district general hospital

This study describes a three-year audit of methicillin-resistant Staphylococcus aureus (MRSA) in a district general hospital and surrounding community. Despite a continuing increase in new cases of MRSA both nationally and locally, and the transfer of patients with MRSA from outside, the hospital remains free from endemic MRSA, albeit with occasional sporadic cases. This is attributed to the presence of a Control of Infection team who have introduced and implemented various policies to control MRSA. These include prompt screening of hospital transfers, an effective topical regimen, attention to environmental cleaning, treatment for established infection, tailored protocol for colonized urinary catheters and an educational programme for staff. Some of these policies have been extended into the community. This report also presents data from 172 cases of MRSA, including carriage rate, infection site, antibiogram, phage-typing, treatment and/or clearance outcome and preliminary evaluation of pathogenicity. A questionnaire has been formulated to assess colonization vs infection. Future strategies will be required if the Status quo is to be maintained.

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection.

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.