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It has been about 100 years since the Spanish influenza pandemic of 1918-19 that killed an estimated 50 million individuals globally. While we have made remarkable progress in reducing infection-related mortality, infections still account for 13 to 15 million deaths annually. This estimate is projected to remain unchanged until 2050. We have identified 4 megatrends in infectious diseases and these are “emerging and re-emerging infections”, “antimicrobial resistance”, “demographic changes” and “technological advances”. Understanding these trends and challenges should lead to opportunities for the medical community to reshape the future. Further inroads will also require broad approaches involving surveillance, public health and translating scientific discoveries into disease control efforts. Key words: Antimicrobial resistance, Demographic changes, Emerging infections, Technological advances

Background. We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. Methods. Trained personnel collected HAI, AMU, and baseline hospital-and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. Results. Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. Conclusions. This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.

Sixty-eight ancestral Mycobacterium tuberculosis isolates were previously identified by using the tuberculosis-specific deletion 1 (TbD1) PCR and mycobacterial interspersed-repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing (Y. J. Sun, R. Bellamy, A. S. G. Lee, S. T. Ng, S. Ravindran, S.-Y. Wong, C. Locht, P. Supply, and N. I. Paton, J. Clin. Microbiol. 42: 1986-1993, 2004). These TbD1 + ancestral isolates were further characterized and typed in this study by IS 6110 restriction fragment length polymorphism (RFLP) typing, VNTR typing using exact tandem repeats (VNTR-ETR), and spoligotyping of the direct-repeat region. To our knowledge, this is the first characterization of this genogroup by multiple genetic markers based on a fairly large sample size. In this genogroup, all spoligotypes were characterized by the absence of spacers 29 to 32 and 34. In addition, VNTR-ETR typing could add further resolution to the clustered isolates identified by MIRU-VNTR, and the combination of MIRU-VNTR and VNTR-ETR, called MIRU-ETR, showed the highest discriminatory power for these strains compared to IS 6110 RFLP typing and spoligotyping alone. However, MIRU-ETR appeared to still cluster some probably epidemiologically unrelated strains, as judged by IS 6110 RFLP divergence. Therefore, a typing strategy based on stepwise combination of MIRU-ETR and IS 6110 RFLP is proposed to achieve maximal discrimination for unrelated TbD1 + strains. This typing strategy may be useful in areas where TbD1 + ancestral strains are prevalent.

The Beijing genotype of Mycobacterium tuberculosis has frequently been found to be associated with drug resistance. Mutation analysis of the genes encoding 16S rRNA ( rrs ) and ribosomal protein S12 ( rpsL ) revealed a high frequency (97/102; 95.1%) of alterations in streptomycin-resistant M. tuberculosis isolates from Singapore, with rpsL K43R being the most common rpsL mutation (82/92; 89%), which was significantly associated with Beijing strains compared to non-Beijing strains (odds ratio=10.88, 95% confidence interval=3.48–34.1). This is the first study to report the association of Beijing strains with the rpsL K43R mutation in STR-resistant M. tuberculosis isolates with de novo resistance, as determined by clustering analysis.

Background Isoniazid (INH) is a highly effective antibiotic central for the treatment of Mycobacterium tuberculosis (MTB). INH-resistant MTB clinical isolates are frequently mutated in the katG gene and the inhA promoter region, but 10 to 37% of INH-resistant clinical isolates have no detectable alterations in currently known gene targets associated with INH-resistance. We aimed to identify novel genes associated with INH-resistance in these latter isolates. Methodology/Principal Findings INH-resistant clinical isolates of MTB were pre-screened for mutations in the katG, inhA, kasA and ndh genes and the regulatory regions of inhA and ahpC. Twelve INH-resistant isolates with no mutations, and 17 INH-susceptible MTB isolates were subjected to whole genome sequencing. Phylogenetically related variants and synonymous mutations were excluded and further analysis revealed mutations in 60 genes and 4 intergenic regions associated with INH-resistance. Sanger sequencing verification of 45 genes confirmed that mutations in 40 genes were observed only in INH-resistant isolates and not in INH-susceptible isolates. The ratios of non-synonymous to synonymous mutations (dN/dS ratio) for the INH-resistance associated mutations identified in this study were 1.234 for INH-resistant and 0.654 for INH-susceptible isolates, strongly suggesting that these mutations are indeed associated with INH-resistance. Conclusion The discovery of novel targets associated with INH-resistance described in this study may potentially be important for the development of improved molecular detection strategies.

The frequency of HLA-DQ antigens in AIDS patients with toxoplasmic encephalitis (TE) were examined. HLA-DQ3 was significantly more frequent in white North American AIDS patients with TE (85.0%) than in the general white population (51.8%; P = .007, corrected P = .028) or randomly selected control AIDS patients who had not developed TE (40.0%; P = .016). In contrast, the frequency of HLA-DQ1 was lower in TE patients than in healthy controls (40.0% vs. 66.5%, P = .027), but this difference did not reach statistical significance when corrected for the number of variables tested (corrected P = .108 for the general white population). HLA-DQ3 thus appears to be a genetic marker of susceptibility to development of TE in AIDS patients, and DQ1 may be a resistance marker. These HLA associations with disease indicate that development of TE in AIDS patients is affected by a gene or genes in the HLA complex and that HLA-DQ typing may help in decisions regarding TE prophylaxis.

Ethambutol (EMB) [(S,S′)-2,2′-(ethylenediimino)di-1-butanol] is a first-line drug used for antituberculosis therapy. It is often used in combination with isoniazid, rifampin, pyrazinamide, and streptomycin. Membrane-associated arabinosyl transferases have been implicated as the targets for EMB (2, 3, 14, 15). The Mycobacterium tuberculosis emb operon is a gene cluster of three contiguous genes, namely, embC, embA, and embB, which encode mycobacterial arabinosyl transferases (26). These enzymes are involved in the polymerization of the cell wall arabinan (4, 6, 9, 24, 25, 32). Inhibition of arabinan synthesis by EMB results in the accumulation of mycolic acids, leading to cell death. Alterations at codon 306 of embB have been identified as being the most common alteration in EMB-resistant M. tuberculosis clinical isolates (8, 12, 17-20, 23, 29). Initial work on 51 EMB-resistant isolates had shown that 89% of these isolates had alterations at residue 306 of embB, but these alterations were not detected in 30 EMB-susceptible isolates (23). A subsequent study confirmed this high frequency of embB306 alterations, with 67% of 75 EMB-resistant isolates having mutations not found in EMB-susceptible strains (19). This led to several groups developing targeted strategies for the detection of embB306 alterations (7, 16, 21, 30). Amino acids within the EMB resistance-determining region of EmbB proteins are well conserved among mycobacterial species, including those from M. tuberculosis, M. leprae, and M. smegmatis (2), and mutations within this region have been detected in EMB-resistant isolates of M. tuberculosis. The aim of this present work was to screen all regions of the embB gene with previously reported mutations in order to assess the contribution of mutations within this gene to EMB resistance in M. tuberculosis clinical isolates from Singapore. Drug susceptibility testing was done using the BACTEC 460 radiometric method (Becton Dickinson, Towson, Md.) (2.5 μg/ml). Twenty-five consecutive M. tuberculosis isolates resistant to EMB and 20 EMB-susceptible isolates from Singapore were collected as previously described (5, 10). DNA extracted from the isolates was analyzed by amplifying four fragments, using the PCR primers shown in Table ​Table1.1. The PCR products were purified (QIAquick PCR purification kit or QIAquick gel extraction kit; QIAGEN) and directly sequenced using the BigDye Terminator sequencing kit and the ABI PRISM 377 automated sequencer (PE Biosystems, Branchburg, N.J.). Confirmation of mutations was done by reamplification and resequencing. TABLE 1. Oligonucleotide primer sequences for amplification of the embB genea IS6110 profiling was done according to standard procedures to determine if the isolates were epidemiologically independent (28). All isolates with the same nucleotide substitutions in this study were deemed to be epidemiologically unassociated as they had distinct IS6110 fingerprints. Overall, mutations in the embB gene were detected in 17 (68%) of the 25 EMB-resistant isolates (Table ​(Table2).2). Mutations at embB306 were detected in 12 of these 25 (48%) EMB-resistant isolates. Notably, all of the 12 EMB-resistant isolates with embB306 mutations were also resistant to isoniazid. All five EMB-resistant isolates with mutations at codon 497 were resistant to at least three antituberculosis drugs. Three isolates monoresistant to EMB had no detectable mutations in embB. TABLE 2. Mutations in the embB gene in clinical isolates of M. tuberculosis This is the first report of a double substitution (ATG→ATM, where M represents the nucleotides A and C), resulting in a Met→Ile alteration at the frequently altered codon 306 of embB in an EMB-susceptible isolate (Table ​(Table2).2). This isolate was resistant to both isoniazid and rifampin. In addition, three other alterations were also detected in EMB-susceptible isolates, G406D and two novel mutations, M423I and A659T. The isolate with the G406N substitution was also resistant to isoniazid and rifampin, while the isolate with the M423I alteration was monoresistant to isoniazid and the isolate with the A659T alteration was monoresistant to streptomycin. In total, alterations in the embB gene were detected in 4 (20%) of the 20 EMB-susceptible isolates (Table ​(Table22). There is a possibility that these mutations may have occurred in susceptible isolates due to cross-contamination of the PCR product, heteroresistance involving mixed cultures, or errors in the susceptibility testing, though every effort was undertaken to avoid this. Alterations in embB in EMB-susceptible isolates at codons other than codon 306 have been documented in only two isolates with the G406D alteration (20) and one isolate with the S347T alteration (8). This paucity of information is due in part to some studies targeting only embB306 (17, 29), several reporting no mutations (1, 12, 19, 23), and others not including EMB-susceptible isolates (22, 31). Interestingly, all three EMB monoresistant isolates in this present study did not have any detectable alterations in embB. In contrast, all 58 EMB-susceptible isolates in this and other studies with embB alterations were resistant to other antituberculosis drugs as well (8, 17, 20, 29). These observations support the hypothesis that a target other than EmbB may exist for EMB which may be activated during combination treatment with other first-line antituberculosis drugs, resulting in susceptibility to EMB (17). Importantly, if all alterations of embB306 are considered polymorphisms, then only a minority of EMB-resistant isolates would be mutated. A similar scenario was observed in studies defining the role of the katG gene in isoniazid resistance in M. tuberculosis. Members of our group and others have shown that the predominant alteration in katG is R463L, which is detected in both isoniazid-resistant and -susceptible isolates and hence is considered a polymorphism and an unreliable indicator of isoniazid resistance (11, 13, 27). Thus, it is imperative for all studies elucidating the molecular mechanisms of drug resistance in M. tuberculosis to include drug-susceptible isolates as controls. Another interesting finding of this study was the presence of resistance to other antituberculosis drugs when alterations of embB were present. Further investigations are necessary in order to understand the involvement of these drugs in the molecular mechanism of EMB resistance. In conclusion, alterations at embB306 may not confer resistance to EMB but may be common polymorphisms in clinical isolates of M. tuberculosis. The clinical significance of this alteration is dubious, and further evaluation of EMB-susceptible isolates from other geographic regions is warranted.

In conclusion, a large body of new information on the biology and immunology of T. gondii has accumulated in the past several years. Much of this is due to the advent of AIDS and the increased funding made available to researchers interested in opportunistic infections in this patient population. These scientific advances have led to a better understanding of the process by which Toxoplasma infects mammalian host cells, molecular biology and biochemistry of the parasite, antigenic structure and immune response to the infection and approaches to be adopted for drug design and therapeutic strategies. Thus, it is through such recognition of the importance of understanding the basic science of an opportunistic pathogen that such advances can be realized.

Screening of 127 isoniazid (INH)-resistant Mycobacterium tuberculosis isolates from Singapore for mutations within the dfrA and inhA genes revealed mutations in 0 and 5 (3.9%) isolates respectively, implying that mutations in dfrA do not contribute to the detection of INH-resistant M. tuberculosis and that mutations within inhA are rare. Thirty-seven (29%) of the 127 isolates had no mutations in any of the genes implicated in INH resistance ( katG , kasA , and ndh ; inhA and ahpC promoters), suggesting that there are new INH targets yet to be discovered.

Genotypic analysis of resistance to isoniazid (INH) in Mycobacterium tuberculosis is complex due to the various genes potentially involved. Mutations in ketoacyl acyl carrier protein synthase (encoded by kasA ) were present in 16 of 160 (10%) INH-resistant isolates (R121K [ n = 1], G269S [ n = 3], G312S [ n = 11], G387D [ n = 1]). However, G312S was also present in 6 of 32 (19%) susceptible strains. kasA analysis contributed marginally to the performance of INH genotypic testing in Singapore. The significance of kasA polymorphisms in INH resistance should be carefully established.

Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting.We report post-transplantation malaria causing elevation of liver enzymes in two recipients.Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal.This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.

Spontaneous bacterial peritonitis (SBP) is a common cause of morbidity and mortality in patients with advanced cirrhosis and portal hypertension. While gram-negative rods and Enterococcus species are the common offending organisms, Salmonella has also been recognized as a rare and atypical offending organism. Atypical features of Salmonella SBP include both its occurrence in cirrhotic patients with immunosuppressive state and its lack of typical neutroascitic response. Diagnosis is often delayed as it requires confirmation from ascitic fluid culture. We report a case of Salmonella SBP occurring in a patient with decompensated cryptogenic cirrhosis with concurrent low-grade non-Hodgkin lymphoma and prior treatment with rituximab. Physicians should be aware of the atypical presentation, especially in cirrhotic patients who are immunosuppressed.

Introduction: Living donor liver transplantation (LDLT) has progressed dramatically in Asia due to the scarcity of cadaver donors and is increasingly performed in Singapore. The authors present their experience with adult LDLT. Materials and Methods: Adult LDLTs performed at the Asian Centre for Liver Diseases and Transplantation, Singapore from 20 April 2002 until 20 March 2006 were reviewed. All patients received right lobe grafts and were managed by the same team throughout this period. Data were obtained by chart review. This study presents both recipient and donor outcomes in a single centre. Results: A total of 65 patients underwent LDLT. Forty-three were genetically related while 22 were from emotionally-related donors. The majority were chronic liver failure while 14% were acute. The most common indication for LDLT was end-stage liver disease due to hepatitis B virus. A total of 22 patients with hepatoma were transplanted and overall 1-year disease specific survival was 94.4%. The mean model for end-stage liver disease (MELD) score was 17.4 ± 9.4 (range, 6 to 40). Six patients had preoperative molecular adsorbent recycling system (MARS) dialysis with 83% transplant success rate. The mean follow-up was 479.2 days with a median of 356 days. One-year overall survival was 80.5%. There was 1 donor mortality and morbidity rate was 17%. Our series is in its early stage with good perioperative survival outcome with 1-month and 3-month actuarial survival rates of 95.4% and 87.3% respectively. Conclusion: The study demonstrates that LDLT can be done safely with good results for a variety of liver diseases. However, with dynamically evolving criteria and management strategies, further studies are needed to maximise treatment outcome. Key words: Donor and recipient outcome, End-stage liver disease, Hepatitis, Hepatocellular carcinoma, Living donor liver transplantation

Strain typing using variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) is a powerful tool for studying the epidemiology and genetic relationships of Mycobacterium tuberculosis isolates. For this study, isolates from 291 patients in Singapore were genotyped by this method. One hundred sixty-six distinct MIRU-VNTR patterns were detected. One hundred sixty-two strains were grouped into 1 of 35 different MIRU-VNTR clusters and 131 isolates were unique. In this sample collection, 9 of the 12 MIRU-VNTR loci were moderately or highly discriminative according to their allelic diversities. The Hunter-Gaston discriminatory index was 0.975, indicating the high power of discrimination of MIRU-VNTR typing. By direct comparisons with previously typed MIRU-VNTR patterns and by genetic relationship analyses, we could identify and clearly define four epidemic groups of M. tuberculosis in our sample, corresponding to the W/Beijing, East-Africa-Indian, Haarlem, and Delhi genotype families. Furthermore, MIRU-VNTR typing was able to clearly distinguish ancestral and modern M. tuberculosis strains as defined by TbD1 genomic deletion analysis. These results indicate that MIRU-VNTR typing can be a useful first-line tool for studying the genetic diversity of M. tuberculosis isolates in a large urban setting such as Singapore.

Objectives: To evaluate rapid molecular approaches for the detection of pyrazinamide (PZA) and ofloxacin resistance, by screening 100 known drug-resistant Mycobacterium tuberculosis isolates. Methods: Mycobacterium tuberculosis isolates were tested for phenotypic resistance to pyrazinamide and ofloxacin using the BACTEC 460 radiometric method and the E-test, respectively. Mutation screening was done by amplifying the pnc A, gyr A, and gyr B genes by the polymerase chain reaction (PCR) and direct automated sequencing. Results: Twelve isolates were PZA-resistant and 8 of 12 (66.7%) isolates had missense mutations or deletions at the pnc A gene, suggesting that mutation or deletion at the pnc A gene is the major molecular mechanism of PZA resistance among the Singaporean isolates. Using the E-test, 48 isolates were resistant to ofloxacin, with minimum inhibitory concentrations of 4 μg/mL or higher. No mutations were observed at the quinolone resistance-determining region (QRDR) of gyr A in all isolates. At the QRDR of gyr B, mutations were present in 1 of 48 ofloxacin-resistant isolates and 0 of 19 ofloxacin-susceptible isolates. Conclusions: In Singapore, genotypic analysis of resistance to PZA and ofloxacin is inadequate and should be complemented by conventional methods.

Seven isoniazid-resistant isolates with mutations in the NADH dehydrogenase ( ndh ) gene were molecularly typed by IS 6110 -based restriction fragment length polymorphism analysis. All seven isolates with the R268H mutation had identical 1.4-kb IS 6110 fingerprints. High-resolution minisatellite-based typing discriminated five of these isolates; two isolates were identical.

The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults.

Novel mutations in NADH dehydrogenase ( ndh ) were detected in 8 of 84 (9.5%) isoniazid (INH)-resistant isolates (T110A [ n = 1], R268H [ n = 7]), but not in 22 INH-susceptible isolates of Mycobacterium tuberculosis . Significantly, all eight isolates with mutations at ndh did not have mutations at katG, kasA , or the promoter regions of inhA or ahpC , except for one isolate. Mutations in ndh appear to be an additional molecular mechanism for isoniazid resistance in M. tuberculosis .

A 30-year-old woman received a cadaveric renal allograft from a donor who was subsequently found to have renal infection due to Histoplasma capsulatum. The recipient had funguria in the early postoperative period and later developed cutaneous manifestations of disseminated histoplasmosis. We report a case of histoplasmosis transmitted via renal transplantation and describe the subsequent 20-year clinical course.

ContextCurrent screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved.ObjectivesTo determine HIV-1 genetic linkage between virus in 2 HIV-1–infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening.Design and SettingCase study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore.SubjectsThe blood donor and the 2 recipients of donor platelets and red blood cells.Main Outcome MeasuresGenetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts.ResultsDirect DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States.ConclusionsTransmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations.

Rifampin (RIF) is a first-line antituberculosis drug. Resistance to RIF, in the majority of cases, has been associated with mutations within an 81-bp RIF resistance-determining region (RRDR) of the rpoB gene, which encodes the β subunit of the RNA polymerase ([8][1]). RIF acts by binding to the β

Acute acquired toxoplasma infection in a pregnant woman may result in a tragic outcome for her offspring. Transmission to the fetus has been limited almost solely to those women who acquire the infection during gestation; the dictum has been that women infected before conception are at virtually no risk unless they are severely immunocompromised by drugs they receive during pregnancy. Recently, increasing numbers of pregnant women who are coinfected with human immunodeficiency virus (HIV) and Toxoplasma gondii and whose immune deficiencies cause reactivation of the latent T. gondii infection, leading to dual infection of the offspring, have been recognized. All of these events occur in the setting of a preventable infection and disease. Recent studies in Western European countries have defined the prevalence of toxoplasma infection among pregnant populations and the incidence of congenital transmission. Similar timely studies have not been done in the United States. Routine serological screening of women during pregnancy, although it can successfully detect the acute acquired infection and thereby allow treatment intended to prevent infection of the fetus, is not conducted in the United States. Since the vast majority of infected newborns have subclinical infection at birth, they go undetected; if not treated, most suffer the unfortunate sequelae of this congenital infection. Thus, whereas screening is mandatory in countries such as France and Austria, in the United States a single serum sample-often obtained either late in the first trimester or during the second or third trimester-is the only source of information on whether the fetus is at risk.

Toxoplasma immunoglobulin E (IgE) antibodies were evaluated in an immunosorbent agglutination assay (ISAGA) and an enzyme-linked immunosorbent assay (ELISA) to determine their usefulness in the diagnosis of acute infection with Toxoplasma gondii. IgE antibodies were not detected in serum specimens from otherwise seronegative individuals, individuals with chronic toxoplasma infection, or infants without congenital toxoplasmosis. In contrast, they were detected in pregnant women who seroconverted during gestation (100% by ELISA, 63% by ISAGA), patients with toxoplasmic lymphadenopathy (96% by ELISA, 88% by ISAGA), infants with signs of congenital toxoplasmosis which prompted serologic testing in the postnatal period (92% by ELISA, 67% by ISAGA), children and adults with toxoplasmic chorioretinitis (36% by ELISA, 18% by ISAGA), and adult patients with AIDS and toxoplasmic encephalitis (33% by ELISA, 25% by ISAGA). In many of the serum specimens, the titer of IgE antibodies detected by the ISAGA were close to or at the positive cutoff value. The duration of detectable IgE antibodies in patients with acute infections varied considerably among individuals but showed a trend toward a briefer duration by the ISAGA than by the ELISA. These results reveal that recrudescence of IgE antibodies in patients with reactivated chronic infection (toxoplasmic chorioretinitis and toxoplasmic encephalitis) may be useful diagnostically and that demonstration of toxoplasma IgE antibodies is a useful adjunct to currently available serologic tests for the diagnosis of acute toxoplasma infection and toxoplasmosis.

Resistance against acute and chronic infection with Taxoplasma gondii in BALB/c and CBA/Ca mice was compared. Intraperitoneal inoculation of either 20, 40, or 80 cysts of the ME49 strain resulted in mortality rates in BALB/c mice of 12% (2 of 17), 50% (6 of 12), and 75% (9 of 12), respectively, within 3 weeks after infection (acute stage). There was no mortality in the CBA/Ca mice for any of the doses. In marked contrast, CBA/Ca mice were highly sensitive to chronic infection with developing toxoplasmic encephalitis; they began dying 2 months after infection with 10 cysts of the ME49 strain, and mortality reached 53% (16 of 30) by the sixth month postinfection. No mortality (0 of 20) was observed in the chronically infected BALB/c mice. CBA/Ca mice had markedly more cysts in their brains than BALB/c mice in the chronic stage. Severe inflammatory changes were observed only in the brains of CBA/Ca mice. Interestingly, in the acute stage (the first 3 weeks), numbers of cysts in the brains were significantly greater in CBA/Ca than BALB/c mice, whereas only BALB/c mice showed mortality in that time period. No inflammatory changes were observed in brains of BALB/c mice during the acute stage of the infection. Thus, resistance against chronic infection appears to be regulated by a mechanism(s) that is different from those conferring resistance against acute infection. There was no difference in gamma interferon levels in sera between CBA/Ca and BALB/c mice during the acute stage. However, during the chronic stage, only BALB/c mice had detectable levels of gamma interferon in their sera.