Fourfold Rise In Titer Research Articles

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV.

Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.

Immunogenicity and Safety of Alternative Influenza Vaccination Strategies in Repeated Seasons in Pediatric Hematopoietic-Cell Transplant Recipients

Abstract Background Pediatric hematopoietic cell transplant (HCT) recipients are at increased risk for morbidity and mortality from influenza infection. Annual influenza vaccination is recommended; however, HCT recipients have diminished immune responses to vaccination. Our recent trial demonstrated that two doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart post-HCT were more immunogenic than two doses of standard dose quadrivalent influenza vaccine (SD-QIV). We assessed the impact of this strategy in a consecutive season post-HCT. Methods The initial trial was a multi-center double-blinded phase II randomized controlled trial comparing two doses of HD-TIV to two doses of SD-QIV in children 3-17 years old given 3-35 months post-allogeneic HCT. Participants completing the initial trial could re-enroll the subsequent influenza season to receive the same two-dose vaccine formulation. Hemagglutinin inhibition (HAI) titers were measured at baseline and 28-42 days following each dose. Injection-site and systemic adverse events were assessed. The immunogenicity endpoints were the post-dose 1 and post-dose 2 geometric mean HAI titers (GMTs) in the second year of participation. Results A total of 170 participants were enrolled in the initial trial, with 65 re-enrolling for a second year (n=33 SD-QIV and n=32 HD-TIV). Post-dose 1 and 2 GMTs were higher for both the SD-QIV and HD-TIV groups in the second year compared the first year (Table 1). In year two, the adjusted geometric mean ratio (aGMR) comparing HD-TIV to SD-QIV was higher post-dose 1 for A/H1N1 (aGMR=1.99, 95% CI:[1.07, 3.68]). The HD-TIV group demonstrated a higher frequency of four-fold titer rise after a single dose compared to two doses of SD-QIV for A/H3N2 (61% vs. 48%) and B/Victoria (77% vs. 65%). Frequency of injection site and systemic reactions were similar between the HD-TIV and SD-QIV groups in year two. Conclusions The post-dose 1 and 2 GMTs were consistently higher for HD-TIV compared to SD-QIV in year two, and aGMR reached statistical significance after a single dose of HD-TIV for A/H1N1. Year two reactogenicity was comparable for both vaccination strategies. Further studies with larger numbers of participants are needed to demonstrate if one or two doses of HD-TIV are needed in subsequent influenza seasons post-HCT when a two-dose vaccination series is given in the first post-HCT season. Table 1. Point estimates and 95% CIs for geometric mean HAI titer, titer ≥1:40, and proportion with ≥4-fold rise from baseline for each vaccine regimen, stratified for each antigen. Also included is the ratio of the observed values (n) to the number of evaluable subjects (N) at each visit. Baseline titers are measured prior to first vaccine dose, post-dose 1 titers are measured 28-42 days following first dose (prior to the second dose), post-dose 2 titers are measured 28-42 days following second dose. Table 1 Note: If 100% achieved seroprotection or seroconversion, “n/a” was entered as a two-sided 95% CI could not be calculated.

Poliovirus type 1 systemic humoral and intestinal mucosal immunity induced by monovalent oral poliovirus vaccine, fractional inactivated poliovirus vaccine, and bivalent oral poliovirus vaccine: A randomized controlled trial

BackgroundTo inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). MethodsWe conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6–10–14 weeks/fIPV at 6 weeks (A); mOPV1 at 6–10–14 weeks/fIPV at 10 weeks (B); mOPV1 at 6–10–14 weeks (C); and bOPV at 6–10–14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FindingsDuring 18 December 2018 – 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91–97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93–98%]) or 10 weeks (96% [93–98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. InterpretationGiven with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FundingU.S. Centers for Disease Control and Prevention.

Serological Evidence of Chikungunya Virus among Acute Febrile Patients in Southern Mozambique.

BackgroundIn the last two decades, chikungunya virus (CHIKV) has rapidly expanded to several geographical areas, causing frequent outbreaks in sub-Saharan Africa, South East Asia, South America, and Europe. Therefore, the disease remains heavily neglected in Mozambique, and no recent study has been conducted.MethodsBetween January and September 2013, acute febrile patients with no other evident cause of fever and attending a health center in a suburban area of Maputo city, Mozambique, were consecutively invited to participate. Paired acute and convalescent serum samples were requested from each participant. Convalescent samples were initially screened for anti-CHIKV IgG using a commercial indirect immunofluorescence test, and if positive, the corresponding acute sample was screened using the same test.ResultsFour hundred patients were enrolled. The median age of study participants was 26 years (IQR: 21–33 years) and 57.5% (224/391) were female. Paired blood samples were obtained from 209 patients, of which 26.4% (55/208) were presented anti-CHIKV IgG antibodies in the convalescent sample. Seroconversion or a four-fold titer rise was confirmed in 9 (4.3%) patients.ConclusionThe results of this study strongly suggest that CHIKV is circulating in southern Mozambique. We recommend that CHIKV should be considered in the differential diagnosis of acute febrile illness in Mozambique and that systematic surveillance for CHIKV should be implemented.

Encephalitis in the Pediatric Population

1. Stephen J. Falchek, MD* 1. *Division of Pediatric Neurology, Alfred I. duPont Hospital for Children/Thomas Jefferson University, Wilmington, DE, and Philadelphia, PA. * Abbreviations: ADEM: : acute disseminated encephalomyelitis CEP: : California Encephalitis Project CNS: : central nervous system CPP: : cerebral perfusion pressure CSF: : cerebrospinal fluid HSV: : herpes simplex virus IVIG: : intravenous immune globulin MS: : multiple sclerosis PCR: : polymerase chain reaction WNV: : West Nile virus Management of encephalitis, which can be fatal, requires understanding of a broad range of causative agents, pathophysiologic mechanisms, clinical syndromes, and outcomes. After completing this article, readers should be able to: 1. Know the many causes of encephalitis, including infectious, parainfectious, and noninfectious disorders. 2. Recognize the clinical features of encephalitis. 3. Be able to conduct a diagnostic investigation of a patient with encephalitis by using clinical and laboratory criteria. 4. Know the anticipated clinical course of different types of encephalitis. 5. Be familiar with the modalities used to treat encephalitis. 6. Understand the factors that influence the outcome in a patient who has encephalitis. The broad definition of the term “encephalitis,” that is, inflammation of the brain , necessitates acknowledgment of the enormous inclusivity of the topic. The most common interpretation of the term implies a direct invasion of the brain by an infectious pathogen, most commonly, viral, fungal, or parasitic. The topic also includes examples of meningitis mediated by bacteria or other agents, which can produce extrameningeal symptoms such as lethargy or seizures, in which case, the combined term “meningoencephalitis” is used. There are also many examples of encephalitis not due to direct central nervous system (CNS) infections. Inflammatory processes due to an acute or chronic illness can result in an acute immune-mediated encephalitis, such as acute disseminated encephalomyelitis (ADEM), lupus cerebritis, and paraneoplastic syndromes. Agents or conditions that produce slowly progressive CNS symptoms, such as tertiary syphilis or “slow viruses” (the prion protein encephalopathies), also are considered examples of encephalitis. Table 1 lists only a limited number of the many pathogens and pathologic conditions that can cause either acute or subacute encephalitis. In this discussion, …

The immunogenicity of a novel A (H1N1) vaccine in HIV-infected children

BackgroundIn October 2009, the United Kingdom Department of Health recommended vaccination of high-risk groups, including children with HIV, with a novel, oil-in-water AS03B adjuvanted Influenza A (H1N1) vaccine (Pandemrix™). There were no published data available regarding the immunogenicity of this vaccine in such children. ObjectivesThis study evaluated the immunogenicity of the adjuvanted Influenza A (H1N1) vaccine in HIV-infected children immunised according to national recommendations and assessed the impact of vaccination on individual CD4 counts and HIV viral loads. MethodsHIV-infected children attending outpatient appointments between 01 November and 31 December 2009 were offered two doses of H1N1 vaccine three weeks apart and a blood test before and 3 weeks after the second dose of vaccine. Serum antibody responses were determined by a haemagglutination inhibition (HAI) assay using standard methods. ResultsOf the 39 children recruited for vaccination, 31 (median age 11.2, range 3.0–17.9 years) received both doses of vaccine and provided pre- and post-vaccination blood samples. Eight children (26%) had baseline HAI titres ≥1:32. After vaccination, 29 children (94%, 95% CI, 78.6–99.2%) had HAI titres ≥1:32 (seroprotection), of whom 27 (87.1%, 95% CI, 70.1–96.4%) had also had a four-fold rise in titres (seroconversion). In the univariate analysis, post-vaccination geometric mean titres (GMTs) were higher among the 21 children receiving highly active anti-retroviral therapy compared with the 10 treatment-naïve children (GMT 406 [95% CI 218–757] vs. 128 [49–336]; P=0.035), but this was no longer statistically significant when adjusted for prevaccine GMTs. There was no significant impact of vaccination on CD4+ T cell count or HIV viral load. ConclusionThe AS03B-adjuvanted pandemic Influenza A (H1N1) vaccine is highly immunogenic and appears to be safe in HIV-infected children.

Mycoplasma pneumoniae infection in a clinical setting

Mycoplasma pneumoniae infection predominantly affects the respiratory tract, although the other organs may also be involved. Previous studies compared the clinical features of patients with M. pneumonia pneumonia to other pathogens and these studies were predominantly adult case series rather than involving children. The objectives of the present study were to compare the clinical features, laboratory, and radiographic findings in children seropositive for M. pneumoniae infection with children tested for suspected M. pneumoniae infection who were seronegative. Using a retrospective review of children who had complement fixation test (CFT) performed for suspected M. pneumoniae infection, children were classified as seropositive if the acute phase serum titer was >or=64, or paired samples taken 2-4 weeks apart showed a fourfold or greater rise in serum titer. In contrast, a patient with an antibody titer <64 or with paired sera showing less than a fourfold rise in titer was considered seronegative. One hundred and fifty-one children were included. Seventy-six children had serological evidence of M. pneumoniae infection and the remaining 75 were seronegative. Children with M. pneumoniae infection were more likely to have fever >6 days duration prior to admission, crackles on auscultation, radiographic consolidation and thrombocytosis at presentation. In addition, M. pneumoniae infection was associated with pneumonia whereas seronegative children were more likely to have upper respiratory tract infection or asthma. Certain clinical parameters could assist in gauging the likelihood of M. pneumoniae infection in children, and thus direct whether antibiotic treatment is needed.

Polymerase chain reaction in comparison with serological tests for early diagnosis of human leptospirosis

The aim of this study was to compare the sensitivity and specificity of polymerase chain reaction (PCR) using two primer pairs and combined with blood culture, immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA), microscopic agglutination test (MAT) and slide agglutination test (SAT) in the diagnosis of human leptospirosis. We analysed 124 serum samples: 60 from patients with confirmed leptospirosis, 20 from patients with other diseases and 44 from healthy individuals. Analysing the first serum sample collected during the first 3-8 days of disease, the sensitivities of the four tests MAT, IgM ELISA, SAT and PCR were, respectively, 69.0%, 79.3%, 72.4% and 62%. In subsequent samples, those same sensitivities were, respectively, 95.4%, 100%, 100% and 72.7% in samples collected from days 9 to 14 and 88.9%, 88.9%, 77.8% and 44.4% in those collected from days 15 to 42. The most specific method (at 100%) was PCR and the least specific (at 89.1%) was IgM ELISA. Although we found PCR to be less sensitive than the serological tests over the course of the disease, our data indicate that PCR was the most sensitive in those initial serum samples presenting no specific antibodies detectable by any of the serological methods tested. We also recommend that PCR can be used in combination with serological tests as we found that this improves the sensitivity of the diagnosis of leptospirosis in the first phase of the disease (93.1-96.5%).

Gramnegative Sepsis mit Jarisch-Herxheimer-Reaktion

Summary Gram-negative sepsis with Jarisch-Herxheimer reaction We present the case of a 25-year-old male patient with gram-negative sepsis due to leptospirosis and Jarisch-Herxheimer reaction after the first dose of an antibiotic. The microscopic agglutination test (MAT) confirmed the diagnosis with a fourfold rise in titer. The epidemiology, clinical features, diagnosis and treatment of leptospirosis are discussed.

Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea.

Pityriasis rosea (PR) is a common papulosquamous skin disorder that is suspected to have an infectious aetiology. We aimed to study the role of human herpesvirus (HHV)-7 and HHV-6 in the pathogenesis of PR. We performed seroepidemiological studies (indirect immunofluorescence test) and polymerase chain reaction (PCR) analysis for HHV-6 and HHV-7 in patients with PR. Seventy-two serum samples and 37 samples of peripheral blood mononuclear cells (PBMC) from 44 patients with PR were obtained. Twenty-five patients with other skin disorders such as drug eruption, urticaria or herpes zoster were studied as controls in the PCR analysis. HHV-7 DNA was detected in 13 of 30 (43%) samples of PBMC of the patients with PR and 14 of 25 (56%) samples of PBMC of controls. HHV-6 DNA was detected in six of 29 (21%) patients with PR and nine of 23 (39%) controls. Thus there was no difference in the prevalence of HHV-6 or HHV-7 in PBMC between patients with PR and those with other skin disorders. In the seroepidemiological study, two cases of at least a fourfold rise in titre and five cases of a fourfold decrease in titre to HHV-7 antibody, and two cases of a fourfold rise in titre and two cases of a fourfold decrease in titre to HHV-6 antibody, were observed in 24 patients with PR. This seroepidemiological study revealed antibody responses consistent with active infection in several PR patients, but the greater proportion of the patients had no definite increase in the antibody titres. We conclude that HHV-7 and HHV-6 may play a part in some patients with PR, but that other causative agents may exist. Further analyses are needed to determine the causative agents of PR.

Potential importance of Legionella Species as etiologies in community acquired pneumonia (CAP)

Large percentages of patients with community acquired pneumonia (CAP) do not have a defined etiology. Between 1992–1993, 99 acute and convalescent sera were collected from patients with CAP of unknown etiology. The sera were tested using an indirect immunofluorescence antibody assay (IFA) against the following antigens: Legionella pneumophila, serogroups 3,5,6 and 7 and L. longbeachae, L. anisa, L. bozemanii and Legionella-Like Amoebal Pathogens (LLAP). A four-fold rise in titer to at least one of the antigens tested, was seen in 14% of patients; 8% to L. bozemanii, 4% to L. anisa, 2% to S. lyticum, 2% to LLAP 10 and 1% each to LLAP 1, 6 and 9. Two patients reacted to several antigens. These results indicate that other species of legionella may be important in the etiology of CAP. L. bozemanii was the organism identified in the majority of these infections. Better diagnostic studies i.e. cultures, serologies and urinary antigen testing, which recognize legionella isolates other than L. pneumophila serogroup 1 need to be developed.

Incidence of leptospiral abortion in Brazilian dairy cattle

We examined dams' paired serum samples and foetal kidneys (histopathologically and attempting leptospiral cultures) from 120 Brazilian Holstein abortions from 10 herds near Sao Paulo, Brazil, in 1996. Leptospiras was isolated from 15 foetuses. The Leptospira interrogans serovar hardjo was obtained from four, pomona from three and wolffi from eight foetuses. Ten of these 15 foetuses showed a four-fold rise in titres between the day of abortion and the second samples taken 15 days later. Fifty-seven other foetuses had histologic evidence of leptospires; 27 of their dams (47%) had four-fold rises in titres. In total, 72 of 120 aborted foetuses had evidence of leptospiral infection.

Spotted Fever Attributable to Rickettsia conorii: Ten Cases Imported from SubSaharan Africa.

Rickettsiae are pleoniorphocic, obligate intracellular bacteria that occur in the form of cocci and fdaments. They are the cause of widespread disease in tropical and temperate parts of the world. Spotted fever attributable to Rickettsia conorii is a zoonosis transmitted to man by the bite of the dog tick, Rkipicephalus ranpineus. Recently, the incidence in endemic areas has been increasing,'.* and cases have been reported in areas where the disease was previously unusual or unknown. Characteristic features of the disease are fever, headache, myalgia, eschar at the site of the tick bite, and maculopapular rash. The illness is similar to Rocky Mountain spotted fever with two main differences: (1) eschar is present in 30-90% of SFRC patient^,^,^ and (2) SFRC is usually milder, although fatalities have occurred.','. During the period 1991-1993, the authors diagnosed ten patients with SFRC. In all cases, the disease occurred after a recent visit to SubSaharan Africa. The diagnosis was made by consideration of clinical and epidemiologic findings (fever, eschar, rash, and recent travel to an endemic area). Serologic testing revealed positive Igh4 titer or a fourfold titer rise to R. conorii by immunofluorescence assay (IFA). The illness had been acquired in all cases during a trip of G14 days (average 10.8) to SubSaharan Ai it accounts for the majority of imported rickettsioses.' Without efforts at risk reduction, the number of travelers at risk for SFRC is likely to increase as more people go on safari in Africa. The presence of an eschar is valuable in making the diagnosis, and its presence is noticed in 30-90% of reported If an eschar is absent, diagnosis of SFRC is more difficult, and causes of febrile exanthem must be considered in the differential diagnosis.The frequencies of fever, rash, eschar, myalgias, and headaches in our patients were similar to those in other published The patient without fever had two eschars,rash,and positive IgM antibodies. One patient presented with pneumonia, an uncommon complication of SFRC.' The increase in serum aspartate aminotransaminase in 40% of our cases is similar to the frequency reported in other series.' SFRC can be confirmed by the isolation of the organism in an eschar or maculopapular lesion by immunofluorescence or by specific serologic assessment

Spotted Fever Attributable to Rickettsia conorii: Ten Cases Imported from SubSaharan Africa.

Rickettsiae are pleoniorphocic, obligate intracellular bacteria that occur in the form of cocci and fdaments. They are the cause of widespread disease in tropical and temperate parts of the world. Spotted fever attributable to Rickettsia conorii is a zoonosis transmitted to man by the bite of the dog tick, Rkipicephalus ranpineus. Recently, the incidence in endemic areas has been increasing,'.* and cases have been reported in areas where the disease was previously unusual or unknown. Characteristic features of the disease are fever, headache, myalgia, eschar at the site of the tick bite, and maculopapular rash. The illness is similar to Rocky Mountain spotted fever with two main differences: (1) eschar is present in 30-90% of SFRC patient^,^,^ and (2) SFRC is usually milder, although fatalities have occurred.','." During the period 1991-1993, the authors diagnosed ten patients with SFRC. In all cases, the disease occurred after a recent visit to SubSaharan Africa. The diagnosis was made by consideration of clinical and epidemiologic findings (fever, eschar, rash, and recent travel to an endemic area). Serologic testing revealed positive Igh4 titer or a fourfold titer rise to R. conorii by immunofluorescence assay (IFA). The illness had been acquired in all cases during a trip of G14 days (average 10.8) to SubSaharan Ai it accounts for the majority of imported rickettsioses.' Without efforts at risk reduction, the number of travelers at risk for SFRC is likely to increase as more people go on safari in Africa. The presence of an eschar is valuable in making the diagnosis, and its presence is noticed in 30-90% of reported If an eschar is absent, diagnosis of SFRC is more difficult, and causes of febrile exanthem must be considered in the differential diagnosis.The frequencies of fever, rash, eschar, myalgias, and headaches in our patients were similar to those in other published The patient without fever had two eschars,rash,and positive IgM antibodies. One patient presented with pneumonia, an uncommon complication of SFRC.' The increase in serum aspartate aminotransaminase in 40% of our cases is similar to the frequency reported in other series.' SFRC can be confirmed by the isolation of the organism in an eschar or maculopapular lesion by immunofluorescence or by specific serologic assessment

Mediterranean Spotted Fever in Central Tunisia.

Mediterranean spotted fever (MSF) is a tick-borne rickettsiosis caused by Rickettsia conorii. The disease was first described in Tunisia by Conor and Brush in 1910.’ However, only a few studies suggested the persistence of this disease in Tunisia.2 Edlinger et a13 emphasized the fact that MSF is one of the travel diseases that can be contracted in many Mediterranean countries, including Tunisia. Harris et a1 also reported boutonneuse fever in American traveler^.^ The investigators retrospectively reviewed the charts of 80 patients with MSF observed from January 1984 to December 1991 in the Internal Medicine and Infectious Diseases Units of Sousse and Monastir University Hospitals in Tunisia. In all cases, diagnosis was based on clinical features and epidemiologic data. Serologic confirmation using indirect immunofluorescence reaction was obtained in 54 cases (68%). A fourfold rise in titer was noted in 43 patients, a seroconversion in five and a titer (> 1/256) was noted in a single sample in the six remaining patients. The investigators included 26 cases, despite the absence of serological confirmation. This was because these cases met the criteria gathered in the diagnostic score chart established by Raoult et al’ for the diagnosis of MSF. Indeed, these cases had a score > 25 because all epidemiologic and clinical criteria selected by Raoult diagnostic score were satisfied. Fifty-nine men and 21 women (sex ratio, 2.8:l) were seen in the above-mentioned units from 1984 to 1991 (the mean was 10 cases per year). The mean age was 36 (range was 6 to 70 years). Forty-seven percent of patients were between 20 and 40 years. Sixty-one percent of patients were rural inhabitants. Seventynine cases (99%) were noted in the hot season (from April to October); 68 of them (87%) occurred from July to October. Forty-nine (61%) patients had dogs in their proximity, and 41 of them reported contact with dogs’ ticks, Rhipicephalus sanguineus. As Table 1 demonstrates, fever, headache, weakness, and myalgia were the most frequently reported clinical symptoms. Clinical presentation was typical of MSF in that presence of the characteristic symptomatic triad (i.e., fever, rash, and “tache noire”) was noted in 70 patients (88%). Fever was present in 78 patients (98%) and was higher than 385°C in 80% of cases. Rash was observed in all patients. The rash was macular in 30% of cases, maculopapular in 55%, papular in 10% of cases, and purpuric in one case. The nature of rash was unknown in 4% of cases. Rash appeared on the third day of disease in 63% of cases and between the fourth and seventh days in 25% of patients. The date of appearance of the rash was unknown in 13% of patients. “Tache noire” was noted in 70 patients (88%). It was the sole manifestation in 61 of 70 patients (87%), and multiple (two or three) in the remaining cases. “Tache noire” was located in various sites of the body, especially limbs (36%), trunk (27%), and wrinkles (22%). White blood cell count was normal in 61% of patients as is shown in Table 2 . Various nonspecific abnormalities were noted. Cutaneous biopsy was performed in eight patients. In seven cases, the biopsy showed inflammatory damage of endothelial cells with perivascular reactional lymphohistiocytic crown, which can be considered highly suggestive of the lesions of MSF. Direct immunofluorescence staining was not performed. Forty-four patients ( ~ S ’ % O ) received antibiotics for more than 48 hours before consultation. Antibiotics were appropriate in only two cases (chloramphenicol). Thus, the investigators had the opportunity to note that previously prescribed p-lactam antibiotics (20 cases), trimethoprim-sulfamethoxazole (1 case), erythromycin (8 cases), lincosamine (11 cases), and aminoglycoside (2 cases) were ineffective in the treatment of MSF. Seventy-eight patients were treated in hospital with tetracyclines (500 mg q.i.d. during 10 days). Two received ofloxacin (200 mg b.i.d. during 5 days). Recovery was noted in all patients. In all cases, fever disappeared within the first 48 hours after appropriate therapy. Several complications occurred, including mild gastrointestinal hemorrhage (2 cases), granulomatous hepatitis (1 case), acute reversible renal failure (3 cases), uveitis (1 case), and meningo-encephalitis (1 case). All patients had a favorable outcome. As emphasized by our series, MSF is still present in central Tunisia. Although serologic confirmation is not available in 26 patients, the investigators firmly believe that these patients should not be excluded from this series because all meet the epidemiologic and clinical criteria of the MSF diagnostic score chart established by Raoult et al. Furthermore, the favorable outcome after tretracycline therapy argues strongly for the diagnosis of MSF. Thus, in this series, 80 cases

Reactivation of Q fever following cardiac surgery.

To determine whether reactivation of Q fever occurs following cardiac surgery 43 patients who had antibodies to Coxiella burnetii were identified pre-operatively. Serum samples were collected 1, 4 to 6, and 24 weeks post-operatively. One patient had active Q fever endocarditis. Seven of the remaining 42 (17%) had a > or = fourfold rise in titres for antibodies to Coxiella burnetii post-operatively. Only two of these seven had an increase in antibody titres for other agents suggesting that the fourfold titre rise for Coxiella burnetii was not part of a polyclonal response. It is concluded that self-limited reactivation of infection may occur among Coxiella burnetii seropositive patients undergoing open heart surgery.

Nosocomial legionnaires' disease: Lessons from a four-year prospective study

We studied all cases of nosocomial pneumonia at our 800-bed tertiary care hospital from September 1983 to September 1987. Of the 813 cases of nosocomial pneumonia, 31 (3.8%) were definite (isolation of organism or fourfold rise in titer) and 21 (2.5%) were possible cases (single or stable antibody titer of ⩾ 1:256) of legionnaires' disease. The definite cases involved a more severe form of pneumonia and a significantly higher mortality rate—64% versus 14% ( p < 0.0009) compared with the possible cases. Despite attempted comprehensive surveillance, only four (13%) of the definite cases of legionnaires' disease were found that would not have been diagnosed if the study were not ongoing. The yield from adequate (4- to 6-week convalescent serum samples) serologic testing was 5%, whereas the yield from sputum culture was 11%. We conclude that targeted surveillance of immunosuppressed patients with nosocomial pneumonia by culture of respiratory tract secretions for Legionella pneumophila is adequate for monitoring for the presence of legionnaires' disease in a hospital.

Coagglutination (COA) test for the rapid diagnosis of cryptococcal meningitis.

Cryptococcus coagglutination (COA) test reagent was prepared locally and showed no cross reactions with different species of bacteria or yeasts or with 75 control sera including 25 that gave positive results for RA factor. We used the COA test to detect cryptococcus antigen in the CSF and we could confirm the diagnosis of 11 out of 115 suspected cases of fungal meningitis; the titre varied from 4 to 128. A four-fold rise in titre confirmed the diagnostic value and a steady fall in titre in three patients on therapy indicated the prognostic value of the test. The earliest confirmation was in a renal transplant patient on the eighth day after onset of symptoms. The COA test was negative with the CSF of 118 patients with chronic meningitis. Cryptococcal colony forming units (cfu) in CSF varied from 100 to greater than 100,000/ml and correlated well with microscopy and with the COA antigen titre in CSF. Four out of the 11 patients who had cryptococcaemia, had 50,000-100,000 cfu/ml in the CSF. Cryptococcus antigen was detected by COA in the serum of all 11 patients, even in those with only 100 cfu/ml in CSF. In the three post-renal transplant patients, who were being monitored regularly, the diagnosis was made early and all three recovered on antifungal therapy with no relapse to date (1-2 years). All the others, including the two primary CNS infections, succumbed to the disease because they presented late for diagnosis and therapy. The cryptococcus COA test is a simple and specific test that can be used as a rapid test to confirm early diagnosis and permit prompt therapy, which should improve the prognosis in CNS and other forms of systemic cryptococcosis. Moreover, it is reproducible and cost-effective, particularly in countries where the latex and other expensive test reagents are not generally available.

Diagnosis of influenza A virus infections by detection of specific immunoglobulins M, A, and G in serum.

The value of immunoglobulin M (IgM) detection in the early diagnosis of influenza A was examined in a prospective study during an outbreak of influenza A/Philippines/2/82 (H3N2) virus infection in February and March 1986. The IgM response was investigated in sera from 64 adults with influenzalike symptoms; we found a fourfold rise in titer or high titers (greater than or equal to 80) of influenza A virus antibodies by the complement fixation test. The IgM response, analyzed by the hemadsorption immunosorbent technique, was compared with the IgG and IgA responses analyzed by an indirect enzyme-linked immunosorbent assay and the hemadsorption immunosorbent technique, respectively. Antigen detection in nasopharyngeal secretions by immunofluorescence was performed for all patients on admission to hospital. Specific IgM was detected in 86% (55 of 64) of the patients with influenza A. In sera from 36% (18 of 64) of the patients it was detected already on admission. Influenza A virus antigen was detected in nasopharyngeal cells by immunofluorescence on admission in 53% (34 of 64) of the patients. A combination of immunofluorescence and IgM results gave a significantly higher diagnostic rate, 69% (P less than 0.01), on admission than did each of the two tests separately. An IgA serum antibody response was seen in 76% (48 of 64) of the cases but did not contribute to any increase in the diagnostic rate. IgM detection by the hemadsorption immunosorbent technique was found to be a valuable supplement for the diagnosis of influenza A in an early phase of the disease.

Impairment of the immune response to influenza vaccination in renal transplant recipients by cyclosporine, but not azathioprine.

Influenza vaccination has been strongly recommended for immunosuppressed renal transplant recipients. However, immunosuppression may lead to impaired antibody responses. We studied the antibody response to an inactivated trivalent influenza vaccine in 59 renal transplant recipients with life-sustaining kidney function: 21 were on cyclosporine and prednisone, 38 on azathioprine and prednisone. Healthy volunteers (n = 29) and patients on hemodialysis (n = 28) served as controls. Despite comparable renal allograft function, cyclosporine-treated patients had a significantly lower immune response against influenza A viruses than azathioprine-treated patients, whether mean antibody levels, fourfold titer rise, or seroconversion to protective titers was analyzed. No significant differences in antibody responses were found between healthy controls and patients on azathioprine. The patients on hemodialysis showed an impaired response to vaccination. However, in contrast to the cyclosporine-treated patients, booster immunization proved valuable in this group.