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The earth is rapidly warming, driven by increasing atmospheric carbon dioxide and other gases that result primarily from fossil fuel combustion. In addition to causing arctic ice melting and extreme weather events, climatologic factors are linked strongly to the transmission of many infectious diseases. Changes in the prevalence of infectious diseases not only reflect the impacts of temperature, humidity, and other weather-related phenomena on pathogens, vectors, and animal hosts but are also part of a complex of social and environmental factors that will be affected by climate change, including land use, migration, and vector control. Vector- and waterborne diseases and coccidioidomycosis are all likely to be affected by a warming planet; there is also potential for climate-driven impacts on emerging infectious diseases and antimicrobial resistance. Additional resources for surveillance and public health activities are urgently needed, as well as systematic education of clinicians on the health impacts of climate change., Competing Interests: Potential conflicts of interest. R. H. reports serving as a part-time consultant for the Medical Society Consortium for Climate and Health. P. J. E. reports payment for expert testimony for the Andrews Law Group, Tampa, FL. R. C. L. reports grants from the Centers for Disease Control and Prevention (CDC; U01-CK000633), royalties for chapters from UpToDate, providing editorial services for the CDC Foundation, and is a board member for Greater Boston Physicians for Social Responsibility. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In 2014, the Centers for Disease Control and Prevention conducted conveyance contact investigations for 2 Middle East respiratory syndrome cases imported into the United States, comprising all passengers and crew on 4 international and domestic flights and 1 bus. Of 655 contacts, 78% were interviewed; 33% had serologic testing. No secondary cases were identified.

Objective: CDC routinely conducts contact investigations involving travelers on commercial conveyances, such as aircrafts, cargo vessels, and cruise ships., Methods: The agency used established systems of communication and partnerships with other federal agencies to quickly provide accurate traveler contact information to states and jurisdictions to alert contacts of potential exposure to two travelers with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) who had entered the United States on commercial flights in April and May 2014., Results: Applying the same process used to trace and notify travelers during routine investigations, such as those for tuberculosis or measles, CDC was able to notify most travelers of their potential exposure to MERS-CoV during the first few days of each investigation., Conclusion: To prevent the introduction and spread of newly emerging infectious diseases, travelers need to be located and contacted quickly.

Background: Japanese encephalitis (JE) vaccine is recommended for travelers to Asia whose itineraries increase their risk of exposure to JE virus. The numbers of travelers with such itineraries and the proportion of those who receive JE vaccine are unknown. We performed a survey to estimate the proportion of US travelers to Asia who receive JE vaccine according to the Advisory Committee on Immunization Practices (ACIP) recommendations., Methods: We surveyed US residents ≥ 18 years old departing on 38 flights to Asia selected through a stratified random sample of all direct flights to JE-endemic countries from three US airports. We asked participants about planned itineraries and activities, sources of travel health information, JE vaccination status, and potential barriers to vaccination. Participants planning to spend ≥ 30 days in Asia or at least half of their time in rural areas were defined as "higher JE risk" travelers for whom vaccination should have been considered., Results: Of 2,341 eligible travelers contacted, 1,691(72%) completed the survey. Among these 1,691 participants, 415 (25%) described itineraries for which JE vaccination should have been considered. Of these 415 higher JE risk travelers, only 47 (11%) reported receiving ≥ 1 dose of JE vaccine. Of the 164 unvaccinated higher JE risk travelers who visited a health care provider before their trip, 113 (69%) indicated that they had never heard of JE vaccine or their health care provider had not offered or recommended JE vaccine., Conclusions: A quarter of surveyed US travelers to Asia reported planned itineraries for which JE vaccination should have been considered. However, few of these at-risk travelers received JE vaccine., (Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)

With advanced air handling systems on modern aircraft and the high level of measles immunity in many countries, measles infection in air travelers may be considered a low-risk event. However, introduction of measles into countries where transmission has been controlled or eliminated can have substantial consequences both for the use of public health resources and for those still susceptible. In an effort to balance the relatively low likelihood of disease transmission among largely immune travelers and the risk to the public health of the occurrence of secondary cases resulting from importations, criteria in the United States for contact investigations for measles exposures consider contacts to be those passengers who are seated within 2 rows of the index case. However, recent work has shown that cabin air flow may not be as reliable a barrier to the spread of measles virus as previously believed. Along with these new studies, several reports have described measles developing after travel in passengers seated some distance from the index case. To understand better the potential for measles virus to spread on an airplane, reports of apparent secondary cases occurring in co-travelers of passengers with infectious cases of measles were reviewed. Medline™ was searched for articles in all languages from 1946 to week 1 of March 2012, using the search terms "measles [human] or rubeola" and ("aircraft" or "airplane" or "aeroplane" or "aviation" or "travel" or "traveler" or "traveller"); 45 citations were returned. Embase™ was searched from 1988 to week 11 2012, using the same search strategy; 95 citations were returned. Papers were included in this review if they reported secondary cases of measles occurring in persons traveling on an airplane on which a person or persons with measles also flew, and which included the seating location of both the index case(s) and the secondary case(s) on the plane. Nine reports, including 13 index cases and 23 apparent secondary cases on 10 flights, were identified in which transmission on board the aircraft appeared likely and which included seating information for both the index (primary) and secondary cases. Separation between index and secondary cases ranged from adjacent seats to 17 rows, with a median of 6 rows. Three flights had more than one index case aboard. Based on previously published data, it is not possible to say how unusual cases of measles transmission among air travelers beyond the usual zone of contact investigation (the row the index case sat in and 2 rows ahead of or behind that row) may be. The fact that several flights had more than one infectious case aboard and that all but two index cases were in the prodromal phase may be of importance in understanding the wider spread described in several of the reviewed reports. Although the pattern of cabin air flow typical of modern commercial aircraft has been considered highly effective in limiting the airborne spread of microorganisms, concerns have been raised about relying on the operation of these systems to determine exposure risk, as turbulence in the cabin air stream is generated when passengers and crew are aboard, allowing the transmission of infectious agents over many rows. Additionally, the characteristics of some index cases may reflect a greater likelihood of disease transmission. Investigators should continue to examine carefully both aircraft and index-case factors that may influence disease transmission and could serve as indicators on a case-by-case basis to include a broader group of travelers in a contact investigation., (Published by Elsevier Ltd.)

Background: In countries with high rates of measles immunization, imported cases of measles represent an important continuing source of measles infection., Methods: Airlines and state health departments report cases of suspected measles in international travelers to the Centers for Disease Control and Prevention Quarantine Stations. We reviewed these reports, maintained in an electronic database, to determine the demographic and epidemiologic characteristics of international air travelers infected with measles., Results: We reviewed 35 confirmed cases of measles in air travelers and analyzed their demographic and epidemiologic characteristics. The median age of case travelers was 17 (range: 4 months-50 years). These travelers arrived from all regions of the world, including 10 countries with immunization rates of measles-containing vaccine below 90% and five others experiencing local outbreaks. Of 17 travelers for whom immunization status was known, 2 had been adequately immunized with at least two doses of a measles-virus containing vaccine, 9 were inadequately immunized, and an additional 6 infants had not been immunized because of age., Conclusions: Measles importations continue in the United States. Travelers should be aware of the importance of assuring up-to-date immunizations, especially when visiting countries experiencing a local measles outbreak. In addition, parents traveling with infants, and their physicians, should be aware of recommendations regarding the early administration of a dose of measles-containing vaccine for infants at least 6 months old traveling internationally., (© 2011 International Society of Travel Medicine.)

Setting: The risk of transmission when persons with active tuberculosis travel on buses or trains is uncertain and no recommendations have been published for contact investigations on these conveyances., Design: We conducted a systematic review of the published studies of tuberculosis transmission among bus or train travelers., Results: Twelve published reports were identified, including one retrospective cohort study and eleven contact investigations. One contact investigation involved train travelers and one involved students on a 6 h bus excursion. The remaining nine involved exposures on school buses or in commuter vans. In eight reports, evidence of tuberculosis infection was found in 8.7%-55% of those tested; six of these studies reported identifying 1-24 cases of active tuberculosis., Conclusions: These reports support the need to be alert to the possibility of tuberculosis transmission on buses or trains. However, they do not offer the quantitative estimate of risk needed for defining policy regarding contact tracing for persons exposed on buses or trains. Decisions to carry out contact investigations should take into account the proximity to the index case, duration of exposure, and other risk factors that may affect the infectiousness of the case or the susceptibility of the contact. Additional reports taking these factors into consideration would help clarify the risk of tuberculosis transmission on public transport., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

To determine the effects of school closure, we surveyed 214 households after a 1-week elementary school closure because of pandemic (H1N1) 2009. Students spent 77% of the closure days at home, 69% of students visited at least 1 other location, and 79% of households reported that adults missed no days of work to watch children.

The Institute of Medicine (IOM) report Quarantine Stations at Ports of Entry: Protecting the Public's Health focused almost exclusively on U.S. airports and seaports, which served 106 million entries in 2005. IOM concluded that the primary function of these quarantine stations (QSs) should shift from providing inspection to providing strategic national public health leadership. The large expanse of our national borders, large number of crossings, sparse federal resources, and decreased regulation regarding conveyances crossing these borders make land borders more permeable to a variety of threats. To address the health challenges related to land borders, the QSs serving such borders must assume unique roles and partnerships to achieve the strategic leadership and public health research roles envisioned by the IOM. In this article, we examine how the IOM recommendations apply to the QSs that serve the land borders through which more than 319 million travelers, immigrants, and refugees entered the U.S. in 2005.

Background: International travelers visiting friends and relatives (VFRs) in lower income countries experience high rates of travel-related infections. We examined demographic characteristics and pretravel preparation practices among US residents traveling to India to determine factors that may contribute to higher infection rates and that would allow for improved prevention strategies., Methods: A cross-sectional study was conducted among US residents traveling to India in departure areas for flights to India at three US international airports during August 2005. Eligible travelers were US residents going to India who were English speaking and >or=18 years. Self-administered questionnaires were used to assess knowledge of and compliance with pretravel health recommendations., Results: Of 1,574 eligible travelers, 1,302 (83%) participated; 60% were male and the median age was 37. Eighty-five percent were of South Asian/Indian ethnicity and 76% reported VFR as the primary reason for travel. More than 90% of VFRs had at least a college education and only 6% cited financial barriers as reasons for not obtaining travel health services. VFRs were less likely than non-VFR travelers to seek pretravel health advice, to be protected against hepatitis A or typhoid fever, and less likely to be taking appropriate antimalarial chemoprophylaxis. However, when stratified by ethnicity, travelers of South Asian ethnicity were less likely than other travelers to adhere to pretravel health recommendations, regardless of VFR status., Conclusions: Similar to previous studies, VFR status was associated with pretravel health practices that leave travelers at risk for important infectious diseases. This association differed by ethnicity, which may also be an important marker of nonadherence to pretravel health recommendations. These findings have important implications for identifying at-risk travelers and properly targeting prevention messages.

A large mumps outbreak occurred among students at a Kansas university in 2006. To reduce transmission, students with mumps were asked to isolate themselves. We describe isolation measures and student compliance with these measures. Questionnaires were administered to students suspected of having mumps. Of the 132 students instructed to stay isolated, 75% stayed isolated for the number of days recommended and were considered compliant. Case-students told to stay isolated for 1-4 days were more likely to be compliant [86% vs. 66%; adjusted odds ratio (aOR) 3.6, 95% CI 1.4-9.0] than those told to stay isolated for 5-9 days. Those who rated avoiding contact with others during isolation as very important were also more likely to be compliant (83% vs. 60%; aOR 3.6, 95% CI 1.5-8.4) than those who rated the importance lower. In a college setting, it may be difficult to achieve high compliance with guidelines recommending that persons stay isolated for much longer than 4 days.

School closure is a proposed strategy for reducing influenza transmission during a pandemic. Few studies have assessed how families respond to closures, or whether other interactions during closure could reduce this strategy's effect. Questionnaires were administered to 220 households (438 adults and 355 children) with school-age children in a North Carolina county during an influenza B virus outbreak that resulted in school closure. Closure was considered appropriate by 201 (91%) households. No adults missed work to solely provide childcare, and only 22 (10%) households required special childcare arrangements; 2 households incurred additional costs. Eighty-nine percent of children visited at least 1 public location during the closure despite county recommendations to avoid large gatherings. Although behavior and attitudes might differ during a pandemic, these results suggest short-term closure did not cause substantial hardship for parents. Pandemic planning guidance should address the potential for transmission in public areas during school closure.

The 1918 "Spanish flu" was the fastest spreading and most deadly influenza pandemic in recorded history. Hypotheses of its origin have been based on a limited collection of case and outbreak reports from before its recognized European emergence in the summer of 1918. These anecdotal accounts, however, remain insufficient for determining the early diffusion and impact of the pandemic virus. Using routinely collected monthly age-stratified mortality data, we show that an unmistakable shift in the age distribution of epidemic deaths occurred during the 1917/1918 influenza season in New York City. The timing, magnitude, and age distribution of this mortality shift provide strong evidence that an early wave of the pandemic virus was present in New York City during February-April 1918.

Phagocytosis may be important in clearing Haemophilus influenzae from the bloodstream. To define the effect of type b capsule on phagocytosis, binding and ingestion by macrophages was measured for 5 isogenic sets of capsule-sufficient strains (clinical isolates and type b transformants of capsule-deficient mutants) and capsule-deficient mutants (strains lacking a 9-kb EcoRI fragment of chromosomal DNA associated with type b capsule expression). Capsule-sufficient strains were not bound in the absence of serum, whereas capsule-deficient strains were bound and ingested (1.8-5.1 organisms/macrophage; 59%-97% ingested). In the presence of nonimmune serum, capsule-sufficient strains were largely bound but not ingested (4.7-7.2 organisms/macrophage; 7%-21% ingested), whereas capsule-deficient strains were nearly all ingested (6.2-10.5 organisms/macrophage; 93%-97% ingested). Strains resisting ingestion caused persistent bacteremia 24 h after intravenous challenge in mice and were more likely than readily ingested strains to cause persistent bacteremia or death in infant rats. Thus, type b capsule inhibits ingestion by macrophages; resistance to ingestion may be an important virulence determinant of type b organisms.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infection. Outbreaks of infection caused by these pathogens are generally considered to be traceable to introduction of single strains into a hospital population. A large outbreak of bacteremic disease that recently occurred in our neonatal intensive care unit (11 episodes in 10 patients) involved 9 low birth weight infants and was associated with serious infection (4 episodes of meningitis). To determine the role of a single point source in this outbreak, isolates were characterized based on phenotypic and genotypic analyses. Phenotypic analysis included assessing hemolytic activity, phage typing, antimicrobial susceptibility testing and methicillin resistance population analysis. Genotypic analysis included assessment of plasmid profiles, dot-blot hybridization, restriction enzyme fragment pattern analysis and hybridization analysis of chromosomal DNA using a panel of staphylococcal gene probes. This analysis established that at least two distinct strains of MRSA were responsible for disease during this outbreak. This experience demonstrates the potential for MRSA to cause severe disease in the neonatal intensive care unit and indicates that the epidemiology of MRSA outbreaks is more complex than the spread of a single strain of bacteria.

To understand how complement effects phagocytosis of type III group B streptococcus, we assessed the specific role of C3 in mediating binding and ingestion of these bacteria by macrophages. Phagocytosis of bacteria by resident mouse peritoneal macrophages was measured under conditions in which C3 deposition on bacteria was inhibited or after blockade of C3-ligands or of complement receptor type three (CR3) with specific antibodies. C3 depletion, incubation with F(ab')2 fragments of antibody to C3, or blockade of CR3 completely inhibited the binding of bacteria that was seen in the presence of nonimmune serum. Immune serum increased the number of associated organisms 6-fold compared to that seen with nonimmune serum. With this serum, 82% of organisms were ingested. C3 depletion or CR3 blockage had a modest effect, but this interaction could be ablated completely only after Fc receptors were blocked. Using varied concentrations of an IgG2a MAb against type III capsular antigen, it was possible to show that small amounts of antibody incapable of mediating bacterial binding by itself directed an interaction that also depended upon C3. Phagocytosis of group B streptococci by macrophages in the presence of little or no antibody requires complement and C3 opsonization specifically. C3-dependent binding may be important in determining mononuclear phagocyte-dependent clearance of these pathogens from blood, particularly in patients with little or no type-specific serum antibody.

Familiarity with the demographics of pediatric HIV disease and recognition of common and uncommon presentations of infection are keys to diagnosing the HIV-infected child. Subsequent management entails preventative care, including immunizations and nutritional support, as well as management of HIV-related complications.

Since 1981, 1200 children with acquired immunodeficiency syndrome have been reported to the Centers for Disease Control. Among these children, Pneumocystis carinii has been the leading cause of serious morbidity and mortality. This review discusses the epidemiology, diagnosis, and treatment of P. carinii.

Previous in vivo studies demonstrated that clearance of encapsulated Haemophilus influenzae from blood is associated with the deposition of C3 on these bacteria and is independent of the later complement components (C5-C9). Since clearance of encapsulated bacteria is determined by phagocytosis of bacteria by fixed tissue macrophages, we studied the interaction of H. influenzae type b with macrophages in vitro. Organisms bound to macrophages in the presence of nonimmune serum. Binding was not evident in heat-treated serum or in serum from complement depleted animals and was inhibited by F(ab')2 fragments of antibody to C3 and by blockade of the macrophage complement receptor type 3. The majority of organisms bound in the presence of complement alone remained extracellular. Antibody in the form of convalescent serum or an IgG1 monoclonal to type b capsule did not increase the total number of organisms associated with macrophages, but did increase the number of organisms ingested. Furthermore, complement enhanced antibody-mediated ingestion. This in vitro study demonstrates that complement largely mediates binding of H. influenzae to macrophages. This binding may be critical in determining the early clearance of these bacteria from blood and may be an important mechanism of defense in the nonimmune, as well as the immune host.

Leishmania are obligate intracellular parasites of mononuclear phagocytes. We and others have shown that the promastigote form of all species of leishmania activates complement from non-immune serum and that this activation can result in parasite lysis. This work, as well as earlier in vivo studies, suggested that complement is an important component of host defence against leishmaniasis. We now present evidence that parasite complement fixation, in addition to increasing parasite phagocytosis, is required for the intracellular survival of leishmania in macrophages. We specifically show a strong correlation between parasite C3 fixation and intracellular survival. We attribute this survival, in part, to a decrease in the magnitude of the macrophage respiratory burst which is triggered by complement-coated, as opposed to uncoated, parasites.

Alkaline phosphodiesterase I activity is demonstrable in lysates of mouse resident peritoneal macrophages (1.43 mU/mg), endotoxin-stimulated macrophages (1.36 mU/mg), and thioglycollate-stimulated macrophages (3.91 mU/mg), as well as in the lysates of several mouse cell lines. The enzyme showed little variation in culture, although serum deprivation caused a 50% decrease in enzyme activity. In each of the three macrophage types about 80% of the enzyme is inactivated by the diazonium salt of sulfanilic acid, indicating that this enzyme is a component of the plasma membrane. In thioglycollate-stimulated cells about the same fraction of enzyme can be inactivated with papain corroborating this assignment. The enzyme is inactivated with a half-time of 14.1 h in resident cells, but this is decreased to 8.2 h in endotoxin cells, and to 5.7 h in thioglycollate cells. These results are consistent with the hypothesis that the endogenous pinocytic rate is a major determinant of plasma membrane turnover. In addition, the different synthetic rates measured in resident and inflammatory cells support the concept that macrophage activation is a differentiative process leading to a qualitatively new cell type.

We studied viral injury to the kidney in a six-year-old boy with hyperimmunoglobulin M immunodeficiency who presented with irreversible acute renal failure and eventually died after five months of dialysis. Renal biopsy at the time of his presentation revealed a predominantly tubulo-interstitial process with numerous viral inclusions that were identified as polyomavirus. Urine cultures showed a massive viruria with BK-type, polyomavirus. The kidney disease was end stage, with persistence of BK virus identified by morphologic techniques and by culture. DNA hybridization analysis showed virus in low concentration in the lymph nodes, spleen, and lungs. The marked viruria, the high concentration of BK virus, and the extensive distribution of viral antigen throughout the kidney all suggest that infection with BK virus was the basis of the severe renal parenchymal injury.

We studied the ability of normal human serum to lyse H. influenzae biogroup aegyptius (H. aegyptius) isolates recovered from patients with Brazilian purpuric fever (BPF clone) or non-BPF clone strains. BPF clone isolates, although similar to non-BPF clone isolates with regard to the ability to fix C3 to their surfaces, could be distinguished from non-BPF clone strains by their resistance to lysis in vitro following incubation with normal adult human serum.

Peritoneal macrophages from mice injected 4 days previously with Brewer's thioglycollate medium have a pinocytic rate, in culture, of 190 ng horseradish peroxidase (HRP)/100 mug cell protein/h, compared to the rate of resident peritoneal cells of 53 ng HRP/100 mug cell protein/h. Mice injected with endotoxin or with only certain of the components of the Brewer's medium show an intermediate level of stimulation. The rate of unstimulated, endotoxin-stimulated, or thioglycollate-stimulated cells shows little change over several days in culture. The pinocytic rate of thioglycollate-stimulated cells can, however, be further increased by exposure of concanavalin A. Although cells may show transient increases in their pinocytic rate in many situations, a sustained increase in pinocytic rate is a sign of the "activated" state of macrophages.

The evaluation of mucosal cellular immune function in the gastrointestinal tract has focused on properties of lymphocytes. We describe methods for use in guinea pig and human tissue that will now permit the maintenance and in vitro study of intestinal macrophages. This study characterizes the resident gastrointestinal macrophage population in the two species and shows that morphologic and ultra-structural characteristics are similar to macrophages from other tissues. Histochemically, the cells are esterase positive and peroxidase negative. They possess surface receptors for immunoglobulin G and complement, and are phagocytic via the Fc receptor.

The half-time for the degradation of horseradish peroxidase (HRP) is increased from 14 h to 37 h in Con A-treated cells, while the half-time for the degradation of [(125)I]BSA is increased from 5.4 h to 14.8 h. This supports prior microscopic observations which suggested that Con A pinosomes showed a marked impairment in their ability to form phagolysosomes. Artifacts due to anomalous behavior of HRP-Con A complexes, or to inhibition of lysosomal hydrolases by Con A, could be excluded. These indications of impaired phagolysosome formation, as well as those described in the preceding paper, could be reversed by postincubation of the cells in mannose, but not in galactose. This reversal is accompanied by a dissociation of Con A-FITC from the inner surface of the pinosome membrane, into the vesicle contents. These observations may be relevant to the ability of Con A to affect several membrane characteristics, and are also of interest in relation to the impaired formation of phagolysosomes which has been described in certain in vitro parasitic infections of macrophages or other cells.

The interaction of fresh serum with promastigotes of Leishmania major, L. donovani, L. mexicana mexicana, L. mexicana amazonensis, and L. braziliensis guyanensis results in lysis of all strains tested with either fresh human or guinea pig serum at 37 C for 30 min. Lysis does not occur in the cold and requires divalent cations and complement that is active hemolytically. Serum deficient in the eighth component of complement is not lytic. Lysis of L. major, L. mexicana, and L. braziliensis proceeds fully in human serum containing EGTA/Mg2+ or in guinea pig serum deficient in the fourth complement component. These species consume only small amounts of C4 from human serum and do not require calcium to optimally bind C3. The data indicate that all are activators of the alternative complement pathway and that the classical pathway is not required for the lysis of these organisms. Promastigotes of L. donovani, in contrast, activate the classical pathway. The presence of calcium is required for both optimal C3 binding and parasite lysis, and L. donovani promastigotes consume C4 when incubated in human serum. In high concentrations, human serum agglutinates all tested Leishmania spp. The agglutinating factor does not require divalent cations, is heat stable, and works at 4 C, suggesting that it is an antibody. This "naturally occurring" antibody cross reacts with all Leishmania spp. and agglutinates them. The adsorption of serum with any Leishmania species or with beads that are Protein A coated, removes the agglutinogen. This factor causes a slight enhancement in alternative pathway activation by L. major and mediates the classical activation by L. donovani. In adsorbed serum, L. donovani promastigotes only weakly activate the alternative complement pathway. Increased concentrations of adsorbed serum are therefore necessary for lysis to proceed. The titer can be partially restored by the addition of heat inactivated serum. Using purified components of the classical cascade, we are unable to visualize surface bound C3 on L. donovani promastigotes unless heat inactivated serum is also present. We conclude that all Leishmania spp. promastigotes are susceptible to lysis by normal serum independent of antibody. The presence of small amounts of naturally occurring antibody in human serum enhances the susceptibility of L. donovani promastigotes to lysis by activating the classical complement pathway.

In summary we are confronted with the awareness that Salmonella organisms of various species have developed simultaneous resistance to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole. These strains are now widespread throughout much of Asia and the Middle East and have caused outbreaks of disease in man and animals in many different countries. Several reports document the appearance of these clinically resistant organisms in the United States, usually as a result of importation from abroad. Since most of the reported cases have been in infants, and given the duration of carriage and the impossibility of adequate hygienic precautions in this age group, secondary spread is to be expected. In this regard the Centers for Disease Control have already noted increased reports of S. mbandaka and S. alachua isolates from the states of Minnesota, Oregon and Washington and have attributed this increase to the infected infants adopted from India. Furthermore current patterns of international social mobility would seem to dictate the inevitability of continued importation of such multiply resistant organisms, especially from Third-World countries. In addition to immigration from abroad the selective pressure of antimicrobial usage in this country might contribute to the emergence of similar resistance patterns. Resistance to ampicillin and chloramphenicol has significantly increased in recent years, and one would expect to see more frequent resistance to TMP-SMX as this drug is used more commonly for the management of otitis media, urinary tract infections and other diseases of high prevalence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amastigote forms of Leishmania major are sensitive to lysis by fresh serum, whereas those of L. donovani are resistant. To understand the basis for this resistance we have examined the interaction of complement with amastigotes of seven strains of leishmania. Complement activation was determined by measuring the ability of amastigotes to consume complement from normal serum and by identifying parasite surface-bound C3. All of the strains that were tested activated complement, including both those that are resistant and those that are susceptible to inactivation by fresh serum. Complement consumption by amastigotes was measured as a decrease in the ACH 50 titers of serum exposed to parasites. L. major, L. donovani, and L. mexicana mexicana (strain 1VLM) amastigotes decrease titers by 35.7, 33.5, and 40.3%, respectively. The binding of C3 to amastigotes was judged qualitatively by immunofluorescence and quantitatively by a C3 radiobinding assay. L. major amastigotes bind an average of 6.6 X 10(4) molecules of C3 per parasite. L. mexicana amazonensis, L. mexicana mexicana, and L. donovani bind an average of 3.9 X 10(4), 5.9 X 10(4), and 3.7 X 10(4) molecules, respectively. In all cases, C3 binding is the result of alternative pathway activation requiring Mg++ but not Ca++. Amastigotes of the disseminating strains of leishmania represent the first example of a group of protozoa that activate early complement components leading to fixation of C3, but that are resistant to inactivation by complement.

A review of anaerobic bacteremia in the Neonatal Intensive Care Unit identified 29 episodes of clinically significant bacteremia occurring over the past 18 years. This experience suggested that certain clinical settings were associated with specific anaerobic infections. Although Gram-positive and Gram-negative anaerobes were isolated with similar frequency, 8 of 12 infants bacteremic within the first 48 hours of life were infected with Gram-positive, penicillin G-susceptible organisms whereas 11 of 17 infants older than 2 days were bacteremic with Gram-negative, penicillin G-resistant anaerobes. Eleven of 17 infants with anaerobic bacteremia associated with necrotizing enterocolitis were bacteremic with Gram-negative anaerobes. Five of 6 infants with anaerobic bacteremia associated with chorioamnionitis were bacteremic with Gram-positive anaerobes. These observations should be considered in making decisions regarding empiric therapy for the newborn at highest risk for anaerobic bacteremia.

In this paper we demonstrate the involvement of the macrophage receptor for advanced glycosylation endproducts (AGE) in the phagocytosis of Leishmania major promastigotes. Blocking of this receptor with the ligand, AGE-BSA, leads to a 50% decrease in phagocytosis relative to controls, and a comparable decrease in the respiratory burst. The inhibition of phagocytosis by AGE-BSA was specific to leishmania. The binding of zymosan or C3bi-RBC and the phagocytosis of IgG-RBC or latex beads was not affected by the presence of AGE-BSA. Blocking of both the AGE receptor and CR3 decreases leishmania binding by nearly 90%, and reduces the respiratory burst by 80%, indicating that the two receptors account for the bulk of L. tropica promastigote recognition and uptake by the macrophage.

Coagulase-negative staphylococci are important causes of bacteremia and focal infections in infants hospitalized in neonatal intensive care units. The medical records and echocardiograms of 58 newborns with persistent Staphylococcus epidermidis bacteremia who were hospitalized in the neonatal intensive care unit at The New York Hospital during the past 5 1/2 years were reviewed, and five infants were identified as having S epidermidis right-sided infective endocarditis. These episodes were associated with placement of umbilical venous catheters in the right atrium, slow resolution of bacteremia, and persistent thrombocytopenia. This experience suggests the role of endocardial trauma resulting from the placement of umbilical venous catheters in the pathogenesis of endocarditis. The increasing importance of coagulase-negative staphylococci as a cause of bacteremia in the newborn may explain the emergence of S epidermidis as an important cause of infective endocarditis in the neonatal intensive care unit. These cases underscore the potential severity of S epidermidis infection in the premature newborn.

A set of quantitative signs of activation, previously developed in studies of inflammatory peritoneal macrophages, has been applied to the study of immunologically stimulated peritoneal cells. Mice that are infected systemically with Bacillus Calmette Guérin (BCG) and then challenged locally with soluble mycobacterial antigens generate populations of cells that spread rapidly in culture, display an elevated pinocytic rate, ingest IgMC-coated sheep erythrocytes, and have diminished levels of 5'-nucleotidase activity. These effects depend on sensitization with live organisms, require secondary antigenic challenge, and develop on the same schedule as does effective cell-mediated immunity. The challenge is antigen specific and cannot be replaced by a nonspecific inflammatory stimulus. Thus, the characteristics of inflammatory macrophages that were previously defined are applicable to the study of immunologically mediated macrophage activation. Cells sharing this pattern of characteristics, whatever their mode of generation, are proposed to represent a distinct class of differentiated macrophages, as compared with the resident macrophage population.

The frequency and clinical significance of Staphylococcus epidermidis isolates from blood cultures of neonates collected during a 17-month period in The New York Hospital neonatal intensive care unit (NICU) were reviewed. Twenty-three episodes of clinically significant S epidermidis bacteremia were detected using the criteria of isolation from 3/3 blood culture bottles from a single culture, or isolation from two or more blood cultures taken at different times, or simultaneous isolation from blood and fluid, pus or vascular catheter. Of these 23 episodes of S epidermidis bacteremia, ten were associated with colonized vascular catheters, and four episodes occurred in infants with necrotizing enterocolitis. Focal S epidermidis infection occurred in ten episodes, and persistent bacteremia occurred frequently in this setting. S epidermidis was the most frequent cause of bacteremia in the Neonatal Intensive Care Unit during the period reviewed. Of the isolates determined to be clinically significant, 74% were resistant to methicillin and cephalothin and 91% were resistant to gentamicin. All isolates were sensitive to vancomycin. In addition to removing vascular catheters suspected of being colonized and searching for potential sites of focal infection, an antibiotic regimen that includes vancomycin should be initiated once significant S epidermidis bacteremia has been recognized in the neonate.