Conference Summaries: ICAAC 2001, IDSA 2001, and ASTMH 2001: Part IV
Conference Summaries: ICAAC 2001, IDSA 2001, and ASTMH 2001: Part IV
Conference Coverage
Editor’s Note: The following summaries represent a selection of papers from those presented at the meetings listed below. It is important to recognize that many of these summaries are extracted only from the published abstract, and it is possible that some of the material presented at the conferences may have differed. The abstracts can be found online at the URLs given. The 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, Ill, Dec. 16-19, 2001; www.icaac.org. The 39th Annual Meeting of the Infectious Diseases Society of America, San Francisco, Calif, Oct. 25-28, 2001; www.idsociety.org. The 50th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Atlanta, Ga, Nov. 11-15, 2001; www.astmh.org.—Stan Deresinski, MD, FACP
| Human Herpes Viruses 6 & 7 |
Reactivation of HHV6a, but not HHV6b, cmv, or HHV7 occurred frequently (65%) in critically ill non-immunocompromised patients. (ICAAC #1121.)
The development of skin rash during the first month after bone marrow transplantation was more common in patients with HHV-6 viremia than in those without (54.8% vs 19.5%; P = 0.001). (IDSA #445.) Three of 20 solid organ recipients with presumed CMV syndrome, but who had no evidence of active CMV replication, did have evidence of HHV6 or HHV7 replication. Ganciclovir had no consistent effect on viral loads of these latter 2 viruses. (IDSA #444.)
| Varicella Zoster Virus |
The protective efficacy of prior varicella vaccination was only 40.5% in an outbreak in a day care center. (ICAAC #1559.)
| Parvovirus B19 |
Investigation of an outbreak of febrile illness in nursing staff was confounded by apparent serological cross reactions between IgM antibody tests for human parvovirus B19 and measles virus. (ICAAC #472.)
Three cases of acute agranulocytosis in immunocompetent patients with parvovirus B19 infection, as well as one case of chronic agranulocytosis associated with persistent infection, are described. (IDSA #398.)
|
Respiratory Syncytial Virus |
The presence of expiratory wheezing distinguished children with RSV infection from those with influenza. (IDSA #412.)
Of 102 infants younger than 2 years of age hospitalized with RSV infection, 72% were due to RSVA and 28% to RSVB. Contrary to prior reports that RSVA is associated with more severe infection, there was no apparent difference in the severity of disease when or in the amount of virus in nasal washes between infection with the 2 strains. (ICAAC #658.)
Almost one third of 191 infants aged 0-3 months with demonstrated RSV infection were subjected to "complete sepsis work-ups" with the resultant identification of only 6 (3.1%) cases of urinary tract infection and 1 (0.5%) case of bacteremia. Complete sepsis workup was associated with a higher rate of antibiotic use, increased hospitalization, and prolonged hospital stay. The authors suggest careful thought be given to the necessity for these evaluations and indicate that, at a minimum, these infants should not be subjected to lumbar puncture. (IDSA #303.)
Of 510 patients at a university student health service with cough of more than 6 days duration in most, 11.2% had evidence of RSV infection, with evidence of Mycoplasma infection in 9.5%, Chlamydia in 8.8%, pertussis in 4.1%, parainfluenza virus type 3 in 2.3% and adenovirus in < 1%. The mean duration of cough in subjects with evidence of RSV infection was 18-19.4 days. (IDSA #409.)
| Influenza & Parainfluenza Viruses |
Epidemiology. Ninety five of 459 (21%) children with acute respiratory tract infection requiring hospitalization had a positive viral culture; 14.7% yielded influenza virus, 45.3% RSV, 10.5% parainfluenza and 29% were other viruses. The attack rates for hospitalization among children < 5 years of age were approximately 21.1, 66.7, and 12.5 per 100,000 for, respectively, influenza, RSV, and parainfluenza. (IDSA #415.)
Twelve of 634 allogeneic stem cell transplant recipients in one institution developed infection with human parainfluenza virus 3 over an 11-week period. Epidemiologic data and sequence analysis demonstrated that these were the result of 6 separate introductions from the community, with 2 infections in clinic patients spreading to 4 other clinic patients and 2 inpatients. (ICAAC #473.)
Vaccination. The ACIP recommends that US travelers to the tropics who are at high risk for complications of influenza and who were not vaccinated during the previous fall or winter, be vaccinated prior to travel. The problem, however, is the availability of vaccine and the fact that the influenza strains circulating at the destination may differ significantly from any vaccine that is available. Thus, analysis of influenza virus isolates since 1998 indicate that Thailand should administer vaccine designed for the southern, rather than the northern, hemisphere in May of each year. (ICAAC #1587.)
Diagnosis. Influenza virus was recovered in culture from 21 of 155 (13.5%) of sputum specimens submitted for routine bacterial culture during an influenza outbreak. The samples were also tested for neuraminidase antigen using the 30 minute Biostar FluOIA for which the sensitivity and specificity proved to be, respectively, 87.5% and 91.1%. (ICAAC #1585.)
In an outbreak of influenza on a US Navy ship, the sensitivity and specificity, relative to culture, of the FluOIA on nasal swab specimens were, respectively, 100% and 63%, while the comparable figures for the QuickVue Test were 65% and 92%. (ICAAC #1586.)
Prophylaxis and Treatment. Households with individuals with influenza (index cases) were randomized to prophylactic oseltamivir administration or to drug administration only in the presence of illness; all index cases were treated. Treatment of both index cases and household contacts was associated with a 10.8% household contact attack rate while treatment of only the index cases was associated with a 28.8% rate. (ICAAC #663.)
Two clinical isolates of influenza H3N2 from among 48 recovered from untreated patients were resistant to neuraminidase inhibitors; both had a substitution of isoleucine for arginine in the HA1 229 residue. (ICAAC #661.)
Clinical Disease. Elevated CPK levels were found in 24 of 249 (10%) of patients with influenza; none had evidence of myocardial injury. (ICAAC #1584.)
Three cases of encephalitis in children with influenza B virus infection were described. (IDSA #159.)
| Picornaviruses |
The plasma half-life of pleconaril in health volunteers is > 170 hours and the drug has no effect on theophylline disposition. (ICAAC #483, ICAAC #486.)
In 2 randomized placebo-controlled clinical trials, pleconaril shortened the mean duration of cold symptoms from approximately 7 days to 6 days. (IDSA #414.) In one study, 1044 patients with symptoms of the common cold during August to October of 2000 were randomized to receive either pleconaril or placebo orally; 67% had evidence of picornavirus infection by PCR on nasal mucus. Pleconaril administration was associated with significantly reduced symptom severity within 12-24 hours of its initiation and a mean 1.5 day reduction in duration of symptoms. (ICAAC #659.)
| Smallpox |
A single vaccination with a 1:10 dilution of the existing US stocks of vaccinia yielded a 70% take rate in healthy previously unvaccinated adults. (ICAAC #UL-12.)
| Human T-cell Leukemia Virus Type 1 |
Three patients who received organs from a donor with HTLV-I infection themselves became infected and developed tropical spastic paraperesis within 2 years of transplantation. (ICAAC #1597.)
| Hepatitis Viruses |
HCV
Patients with chronic HCV infection were randomized to treatment for 48 weeks with peg-interferon (a-2a) given weekly in doses of either 180 mg or 135 mg or to treatment with thrice-weekly interferon (at a dose of 3 million units). Sustained (week 72) virologic response were 28% for each of the peginterferon treatment arms, but only 11% (P = 0.002) in the standard interferon arm; histological responses were seen in 58%, 48%, and 45%. Sustained virologic responses in patients infected with genotype 1 were, respectively, 22%, 19%, and 7%. Thus, both pegylated interferon regimens were virologically superior to the standard interferon regimen and the higher dose pegylated interferon therapy was superior, in terms of histological response, to either of the other 2 regimens. (ICAAC #457.)
In a case-control study, liver transplant recipients with HCV infection were more likely than recipients who were not HCV infected to have a major episode of bacterial infection and to have late (more than 6 months after surgery) infections. (ICAAC #749.)
HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk of early fibrosis upon recurrence of HCV infection. (ICAAC #461.)
HHV6 and CMV infection were not associated with HCV recurrence after liver transplantation, except in a subgroup of patients with clinically severe HCV recurrence for whom there was an association with HHV6 viremia. (ICAAC #462.)
HCV/HIV
HIV viral load was positively correlated with HCV viral load in coinfected patients. (ICAAC #747.) Hyperglycemia occurred more frequently in HAART recipients who were HIV/HCV coinfected than in those infected with only HIV in a case-control study. (ICAAC #740.)
HCV coinfected ART-naïve patients initiating HAART have blunted CD4 responses but virologic responses similar to those not coinfected. (ICAAC #205.) HCV infection appeared to increase the risk of hepatic toxicity in patients receiving NNRTIs. There was no difference in risk between efavirenz and nevirapine. (ICAAC #208.)
Thirty five HIV/HCV coinfected patients, 18 with genotype 1, 32 of whom were receiving ART, were treated with PEG-IFN-2b (50 mg q.wk.) plus ribavirin (800 mg b.i.d). At 24 weeks, 6 of 18 (33%) patients were HCV RNA negative and 55% had normal transminase levels. The investigators concluded that higher dose therapy is indicated. (ICAAC #458.)
Five of 22 HIV/HCV coinfected patients developed acute pancreatitis within several months of initiating therapy with interferon and ribavirin; all 5 were receiving stavudine and 4 were also taking didanosine. (ICAAC #739.)
High-dose consensus interferon alpha (15 mcg qd for 4 weeks followed by 15 mg TIW for 44 weeks) of HCV/HIV coinfected patients who failed a previous course of interferon was associated with a 9.4% sustained viral response rate. (ICAAC #459.)
Five HIV-infected patients with decompensated cirrhosis due to HBV and/or HCV infection underwent orthoptic liver transplantation have survived, to the time of the report, a mean of 10.8 months. All 5 were on HAART with undetectable plasma viral RNA in 4 and CD4 counts remaining > 100 cells/mm3. One patient each recovered from acute rejection and wound infection; none had an AIDS-associated opportunistic infection. Two patients had tacrolimus toxicity as a consequence of a pharmacokinetic interaction with protease inhibitors.
HCV/HBV Coinfection
Among a large number of individuals whose only HBV serological marker was a positive test for anti-HBc 53.4% were HCV antibody positive. (ICAAC #756.)
HBV
Five hundred fifteen patients with chronic HBV infection were randomized to receive either placebo or 1 of 2 doses of adefovir. Adefovir 10 mg q.d. treatment for 48 weeks, relative to placebo, was associated with greater likelihood of improvement in liver histology (53% vs 25%), normalization of ALT (48% vs 16%) and of HbeAg seroconversion (12% vs 6%), as well as a greater reduction in plasma HBV DNA (-3.52 log10 vs -0.55 log10). Adefovir 10 mg was as well tolerated as placebo. (ICAAC #LB-20.)
HEV
Hepatitis E virus-like agents were recovered from rats (Rattus norvegicus) in Los Angeles. (ASTMH #56.)
| Geographic & Travel Medicine |
Travel Advice
Ninety nine of 100 Southern California travel agents failed to spontaneously provide health-related advice to an investigator requesting a package adventure tour of 3 weeks to the Brazilian Amazon jungle. After an initial prompt requesting advice, 30% gave general information and one half of that group suggested that shots might be necessary and one half suggested seeking the advice of a physician or consulate. More responded to a second prompt, but 34% still did not mention health measures of any kind. (ASTMH #125.)
The Febrile Patient
A diagnosis was made in 298 of 381 (78.2%) febrile episodes in 368 travelers who returned from the tropics and a travel-related illness was the cause of fever in 84%. Of travel-related illnesses, 70% were due to "tropical" diseases, with the 5 leading causes among this group of 174 being malaria (122), bacillary dysentery (18), typhoid or paratyphoid (9), rickettsiosis (8), and Katayama fever (8). Among the leading cosmopolitan causes were infections due to EBV, CMV, and M tuberculosis. Three patients died, 2 of cerebral malaria and one of multidrug- resistant tuberculosis. (IDSA #251.)
Examination of 370 consecutive febrile nonsurgical patients presenting to a medical center in Katmandu found that 40% had respiratory tract infection (29% lower and 11% upper), 25% had enteric fever, 17% urinary tract infection, 8% murine typhus, 5% leptospirosis, and 1.6% scrub typhus. Six (1.6%) were HIV infected. (ASTMH #45.)
Typhoid Fever
A cluster of cases of typhoid fever in men who had not traveled outside the United States was found to be sexually transmitted, and was traced to a single carrier. (IDSA #936.)
A study in Pakistan found that typhoid fever (treated, that is) did not adversely affect pregnancy outcome. (IDSA #9.)
Clinical and microbiological failure of treatment of typhoid fever with ciprofloxacin was seen in 7 of 122 (5.7%) in Vellore, India. The S typhi isolates in these patients, although still considered susceptible to ciprofloxacin, had MICs at the upper range of "susceptibility" (0.25-1.0 mg/mL). (IDSA #258.)
Brucellosis
The seroprevalence of brucellosis in 592 Egyptian camels from North Sinai Province was 1.7% and was 0.09% in 330 humans. All 3 seropositive humans were nomads who cared for camels, sheep, and goats. B melitensis was isolated from the milk of 2 seropositive camels. (ASTMH #119.)
The median time to serological cure (titer < 1:320) in 116 patients treated for acute brucellosis in an endemic area was 18.5 months. (ICAAC #1401.)
Spirochetes
Studies in southeast Asia (Jakarta, Vientiane, Lao PDR, Hanoi, An Giang) found that 16.5% of patients with acute non-A-E hepatitis had serological evidence of recent leptospirosis. A study of nonmalarial febrile illness in Irian Jaya found evidence of acute leptospirosis in 13% and an evaluation of patients with hemorrhagic fever in Phnom Penh found leptospirosis in 3%. (ASTMH #46.) One fourth of 300 patients presenting with an acute febrile illness to the Kwai River Christian Hospital on the western border of Thailand with Myanmar had serological evidence of acute leptospirosis. (ASTMH #419.)
The annual incidence of leptospirosis in Israel from 1985-1999 was 0.05 per 100,000 population; 29% were due to L ictohaemorrhagica and these occurred exclusively in urban dwellers, most of whom did not have an at-risk occupation. (ASTMH #439.)
A targeted penicillin-based treatment regimen decreased the prevalence of yaws in an endemic community in Guyana by 71%. (ICAAC #1555.)
Rickettsia
A study in Irian Jaya found that 20% of febrile patients absent evidence of malaria had serological evidence of murine typhus, while 5% had evidence of scrub typhus, and 11% of spotted fever. Only 1.1% of children with hemorrhagic fever had evidence of scrub typhus while 0.9% had spotted fever. (ASTMH #49.)
A retrospective review of 55 patients with Rocky Mountain Spotted Fever in 7 Mexican states between 1981 and 2000 found a case-fatality rate, among those for whom outcome was known, of 50%. (ASTMH #765.)
Protozoa
Babesiosis. Two cases, one in Rhode Island, one in New York City, of transfusion-related babesiosis were described. (IDSA #168, IDSA #169.)
Ten of 18 (56%) asymptomatic blood donors who were seropositive for exposure to Babesia microti and who were prospectively followed had a positive PCR for this organism and in 3 of the 10, PCR was positive during at least 1 subsequent visit as well. Three of the PCR- positive subjects were also positive by animal inoculation. All blood smears were negative. (ASTMH #755.)
Leishmaniasis. A review of 42 travelers presenting to the Hospital for Tropical Diseases in London with cutaneous leishmaniasis found that the diagnostic sensitivity of PCR was 90%, granulomas in a biopsy specimen 100%, amastigotes in biopsy 67%, amastigotes in direct microscopy 57%, and culture 38%. (ASTMH #39.)
Six of 12 Peruvians who with cutaneous leishmaniasis that had persisted despite treatment with Glucantime were cured and 6 had marked clinical improvement with the addition of topical imiquimod to their regimen. (ASTMH #777.)
Trypanosomiasis. As previously discussed in Infectious Disease Alert (see July 15, 2001), there has been an increase in the number of travelers to the Serengeti National Park in Tanzania who have developed African trypanosomiasis. (ASTMH #48.)
The seroprevalence of Chagas disease in Coloma, Mexico, was 5%, with the greatest risk in rural and suburban houses in the central zone. (ASTMH #785.) The Chagas seroprevalence rate among school-age children in the endemic area of Guatemala was 5.3%; one fifth of communities had rates of 10-45%. (ASTMH #786.)
Toxoplasmosis. Detection of high-avidity IgG antibodies against T gondii by the enzyme-linked fluorescent assay (ELFA) technique (bioMerieux) "essentially rules out infection having occurred within the 4 prior months." (IDSA #181.)
Malaria. Two hundred two US Foreign Service personnel attached to US embassies were reported to have developed malaria from 1995-2000; two thirds were due to P falciparum. Infection was acquired in Africa, the majority of these in western Africa, in 88.6%. Two thirds of the total reported no chemoprophylaxis. (ASTMH #530.)
Ten percent of 186 children with febrile seizures in Ghana were found to have bacterial meningitis, while 16% had cerebral malaria. (ASTMH #40.)
The mean sensitivity, specificity, and positive predictive value for the diagnosis of malaria by microscopists at secondary health care facilities in Benin were, respectively, 92%, 52%, and 42%. The rate of false positivity was 48% and of false negativity was 8%. (ASTMH #546.) Prior to a successful 4-day intensive training course, 24 experienced microscopists in Kenya demonstrated slide reading sensitivity ranging from 40% to 100% and specificity ranging from 0% to 100%, with a mean of 79% for both. Microscopists with more than 5 years of experience had a mean reading specificity of 15%. (ASTMH #248.)
A randomized trial in children in Mali found that trimethoprim/sulfamethoxazole had 94% prophylactic efficacy against clinical malaria. (ASTMH #361.) Atovaquone/proguanil was well tolerated and highly effective in the prophylaxis of P falciparum infection in a placebo-controlled randomized trial of 330 children in Gabon. In addition, atovaquone/proguanil did not impair the immunogenicity of oral live attenuated typhoid vaccine (Ty21a) or of an oral cholera vaccine (CVD103-HgR). (ASTMH #580.)
Nonimmune children (221) traveling to a malaria endemic area for up to 28 days were randomized to receive prophylaxis with either atovaquone/proguanil or chloroquine. No cases of malaria occurred in either group. Malarone was somewhat better tolerated than was chloroquine in this open-label study. (ASTMH #579.)
In a randomized trial in Australian soldiers in East Timor, 3 days of tafenoquine administration had efficacy similar to that of 14 days of primaquine administration as terminal malaria prophylaxis. (ASTMH #233.)
Ninety eight patients in India with P vivax infection were randomized to treatment with either azithromycin 1000 mg q.d. for 3 days or a standard regimen of chloroquine—each followed by primaquine for 14 days beginning at day 7. At day 7, parasite clearance had been achieved in 84% of azithromycin and 98% of chloroquine recipients; the median times to parasite clearance were, respectively, 4 days and 2 days (P < 0.0001). (ASTMH #228.)
The 28-day cumulative risk of failure of chloroquine therapy of P vivax infection was 27% in western Indonesia and 52% in eastern Indonesia. Failure to clear parasitemia by day 4 had a 100% sensitivity and 70% specificity in predicting therapeutic failure. (ASTMH #597.) Two patients in Sumatra had malaria due to chloroquine-resistant P malariae. (ASTMH #367.)
Halofantrine treatment of nonimmune children with malaria, mostly acquired in West Africa, was associated with a high risk of relapse in the younger subjects and in those with diarrhea. (ICAAC #1136.) Chloroquine plus dapsone was effective in the treatment of malaria due to P falciparum that was resistant to pyrimethamine/sulfadoxine in children in Tanzania. (ASTMH #809.) Chlorproguanil/dapsone daily for 3 days was more effective than a single dose of pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in children in Africa (Kenya, Malawi, Tanzania, Nigeria, Gabon). (ASTMH #810.) Atovaquone/proguanil was safe and highly effective in the treatment of P falciparum malaria in children in Gabon who weighed > 5 kg and < 10 kg. (ASTMH #813.)
Self-treatment of malaria with atovaquone/proguanil was tolerated and successful in 7 travelers to remote areas. (ASTMH #582.)
In the absence of a single adequately powered randomized trial, a meta-analysis found that exchange transfusion does not appear to increase survival in patients with severe malaria due to P falciparum. (ASTMH #42.)
Amebiasis. Examination of 471 adults with amebic liver abscess and 107 with pyogenic liver abscess by logistic regression analysis found that age older than 50, male gender, and the presence of multiple abscesses were predictive of pyogenic infection. (ASTMH #348.)
Microsporidioisis. Ten AIDS patients and 2 organ transplant recipients with intestinal microsporidiosis were randomized to receive fumagillin or placebo. The organism was eliminated from stool in all 6 fumagillin recipients but none given placebo. (ICAAC #1135.)
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