Summaries from the 36th Meeting of the Infectious Disease Society of America: Pa
Summaries from the 36th Meeting of the Infectious Disease Society of America: Part II
conference coverage
Note: The following summaries represent a selection of papers from those presented at the 36th Meeting of the Infectious Disease Society of America (IDSA), held November 12-15, 1998, in Denver. 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 conference may have differed. The abstracts are available at http://www.marathonmultimedia.com/abstracts/idsa.— Stan Deresinski, MD, FACP
HIV Infection and Its Complications
Antiretroviral Therapy. Inadherence to prescribed therapy is the bane of HIV management. Several methods of attempting to improve adherence with antiretroviral therapy were described, including daily delivery of medications, use of the medication via electronic monitoring system (MEMS), and use of a two-way electronic pager. (Abstracts 487-489.) These methods had varying degrees of success and practicality.
The sequence in which drugs are used may play a role in the likelihood of a favorable antiretroviral effect. Prior d4T therapy impairs the response to subsequent therapy with ZDV. In contrast, starting with ZDV and then changing to d4T was not associated, after 12 months of therapy, with less impairment of virologic response. (Abstract 475.) ZDV-experienced patients who fail to respond to d4T have significantly more RT resistance mutations than do responders, suggesting that this phenotypic resistance is not, as has been previously suggested, due to an antiretroviral-induced change in host cellular kinase levels. (Abstract 473.) Similarly, it was reported at the recent Glasgow meetings that d4T treatment may be associated with the ZDV-associated mutations at positions 215 and 70. (A summary of the Fourth International Congress on Drug Therapy in HIV Infection, held November 8-12, 1998, in Glasgow, Scotland is available at http://www.healthcg.com/hiv/confs/glasgow98.)
Resistance to d4T has previously been demonstrated to be only inconsistently associated with an RT gene V75T mutation and, more recently, with insertions at or near codon 69, most commonly 69S (-S-S) together with ZDV resistance-associated mutations. A new study found that the presence of the I178M RT mutation is associated with failure of d4T therapy. (Abstract 474.)
The management of patients failing antiretroviral therapy continues to strain the ingenuity of clinicians dealing with an expanding, but still limited, armamentarium. A study of factors associated with success after modification of therapy in 96 patients failing treatment with at least two drugs was reported. Success, defined as a more than 0.5 log10 decrease in viral load at 3-12 weeks after modification, was observed in 56 (58%) and was associated with the addition of at least two new drugs, adding a drug from a previously unused class, adding any new NNRTI, but not substituting a PI. The use of the results of a commercially available genotypic resistance assay was not associated with an improved outcome. (Abstract 445.)
Thirty-one patients with a viral load of more than 2500 copies/mL who were ddI naïve, had received less than six months of d4T, and were PI (other than nelfinavir) experienced were given ddI, d4T, and nelfinavir. The mean viral load decreased from 22,840 copies/mL 1.20 log10 to a nadir value of 1428 copies/mL, without a significant increase in CD4 count. (Abstract 442.) The evidence of persistent viral replication, however, bodes ill for the durability of this response.
Experiences with a variety of other salvage regimens were reported, with varying results, largely depending upon the specifics of prior failed therapy. These regimens included: ritonavir + saquinavir + nevirapine; adefovir + abacavir + efavirenz; efavirenz + abacavir; hydroxyurea, usually with ddI; "intensification" by addition of abacavir; and abacavir + amprenavir + efavirenz. (Abstracts 437, 438, 440, 441, 444.) Protease inhibitor experienced patients given the last mentioned regimen resulted in only 15% of patients achieving a plasma viral load less than 400 copies/mL at 16 weeks. (Abstract 441.)
Abacavir is a potent nucleoside analog RT inhibitor that was recently approved by the FDA. Fifty-five antiretroviral-naïve patients initially received abacavir alone for 24 weeks when ZDV and 3TC were added to their regimen. The addition of these two drugs significantly improved virologic response so that, at 72 weeks, 50% of patients had viral loads less than 50 copies/mL. (Abstract 446.)
"Intensification" by the addition of abacavir to stable background therapy in patients with CD4 of more than 100 and viral load 400-50,000 copies/mL was generally well tolerated, except for two cases of hypersensitivity reaction, and resulted in a significant decrease in viral load at 16 weeks. This virological response was observed regardless of prior 3Tc therapy and, in fact, the presence of the 3TC associated mutation M184V, appeared to be associated with an improved response. However, the response to abacavir was reduced in the presence of three or more ZDV resistance-associated mutations with or without M184V. (Abstract 440.)
The adverse effects associated with efavirenz use in 413 adults were reported. CNS side effects were observed in approximately one-half the patients but were usually mild-to-moderate and resolved with persisting drug administration, causing discontinuation in only 2.6%. When only treatment-related adverse events of Grade 2 or greater severity are examined, dizziness was reported in 9%, headache in 3%, and impaired concentration in 5%; the same symptoms were reported by, respectively, 2%, 3%, and 2% of control patients receiving regiments not containing efavirenz. CNS symptoms usually began within the first day of efavirenz administration, lasted a median of 2-3 weeks and were moderated by taking the drug at night. Rash was noted in 28% of efavirenz recipients and in 18% of controls, but was of Grade 2 or greater severity in only 11% of the former group (vs 5% of controls). The rash generally began early during therapy, was not dose-related, and led to drug discontinuation in 1.7%. There has been only one case of Stevens-Johnson syndrome among 2200 efavirenz recipients. Elevation of ALT to five times the upper limit of normal or greater was observed in 1.2% of efavirenz recipients and 1.9% of controls who were not HCV infected. Such elevations occurred in two of 12 HCV antibody-positive efavirenz recipients and in none of 10 similar controls. (Abstract 484.)
The administration of rhIL-2 to some HIV-infected patients was associated with the development of hypothyroidism. (Abstract 486.)
Several studies of pharmacokinetic drug interactions were reported. Coadministration of indinavir and nelfinavir results in no change in the pharmacokinetics of the latter but significantly increases levels of the former. The administration of 1200 mg of indinavir and 1250 mg of nelfinavir, each 12 hourly, resulted in Cmax and AUC of the former comparable to that seen with administration of indinavir 800 mg q 8 h without nelfinavir. (Abstract 464.)
Efavirenz is a substrate for and a modest inducer of CYP3A4, as well as a substrate for 2B6. Rifabutin is an inducer of CYP3A4. Consistent with previous reports, coadministration of efavirenz with rifabutin resulted in a modest decrease in plasma concentrations of the latter, but no effect on efavirenz concentrations. It may be feasible to increase the dose of rifabutin by 50% when given with efavirenz. (Abstract 461.) DuPont Pharmaceuticals reviewed the available data on drug interactions with efavirenz; their summary is contained in the table. (See Table.) (Abstract 460.)
| Table | |||||
| Summary of Studies of Efavirenz Drug Interaction Study Results | |||||
| Study Drug | on Efavirenz |
Recommendation | |||
|
|
|
|
|
||
| Amprenavir |
|
|
Uncertain.
Efavirenz levels may be increased relative to historical controls. |
Uncertain.
Efavirenz levels may be increased relative to historical controls. |
While it is likely that amprenavir dose adjustment may be necessary, no specific recommendations are available. |
| Indinavir |
|
|
|
|
Increase indinavir to 1000 mg tid. |
| Nelfinavir |
|
|
|
|
No adjustments. |
| AG-1402 metabolite |
|
|
|||
| Ritonavir: AM dose |
|
|
|
|
No adjustments. |
| Ritonavir: PM dose |
|
|
No adjustments. | ||
| Saquinavir (sgc) |
|
|
|
|
Saquinavir not recommended as sole PI with efavirenz.
No adjustment of efavirenz. |
| Lamivudine |
|
|
|
|
No adjustments. |
| Zidovudine |
|
|
|
|
No adjustments. |
| Azithromycin |
|
|
|
|
No adjustments. |
| Clarithromycin |
|
|
|
|
Consider alternative to clarithromycin.
No adjustment of efavirenz. |
| 14-OH clarithromycin |
|
|
|||
| Ethinyl estradiol |
|
|
|
|
No adjustments, but barrier methods
should be used. |
| Fluconazole |
|
|
|
|
No adjustments. |
| Rifampin |
|
|
|
|
No adjustments. |
| Rifabutin |
|
|
|
|
At least 50% increase in rifabutin dose.
No adjustment of efavirenz. |
| Mylanta DS |
|
|
|
|
No adjustment of efavirenz. |
| Famotidine |
|
|
|
|
No adjustment of efavirenz. |
|
(1) AUC0-24 hours. (2) No change compared to data reported in the literature. (3) No change compared to historical data. Source: 36th Meeting of the Infectious Disease Society of America, Denver, CO, November 12-15, 1998; Abstract 460. __________________________________________________________________________________________ |
|||||
The administration of nevirapine to patients on methadone maintenance resulted in methadone withdrawal symptoms. (Abstract 463.)
There was a paucity of new information regarding opportunistic infections in HIV-infected patients. Eighty-two HIV-infected and 341 non-HIV infected patients were treated for tuberculosis for six months (INH, RIF, PZA, ETH daily for 2 weeks followed by the same drugs twice weekly for 6 weeks, and then INH, RIF twice weekly for 4 months—all directly observed). Treatment response was similar in the two groups. Three (5.8%) of 52 assessable HIV-infected patients relapsed compared to four (1.6%) of 247 non-HIV infected patients (P = 0.10). (Abstract 89.)
A retrospective analysis of 123 HIV-infected patients with disseminated MAC infection found that the use of MAC prophylaxis was associated with an increased risk of death (hazard ratio 2.22; 95% CI [1.34, 3.69]). (Abstract 423.) The reason for this observation was unclear, but it may have been related to unrecorded severity factors used by clinicians in choosing candidates for MAC prophylaxis.
Multivariate logistic regression analysis found that a history of fungal OI was associated with an increased risk of coccidioidomycosis in HIV-infected patients, while being white was protective. Analysis of the subgroup of patients (including controls) of patients with a history of fungal OI, found that receipt of an azole antifungal agent in the three months prior to enrollment was protective. (Abstract 343.) This suggests to the investigators the hypothesis that patients living in an endemic area may be chosen for prophylaxis against the development of coccidioidomycosis based upon evidence of recent need for antifungal therapy.
Following serum cryptococcal antigen titres in AIDS patients with cryptococcal infection was not useful in a retrospective study of 136 patients. (Abstract 335.)
Joining an ever-growing list, chronic parvovirus B19 infection resolved after institution of HAART in one patient. (Abstract 499.)
Respiratory Tract Infections
A five-day course of prednisone (2 mg/kg/d) did not interfere with the antibody response to influenza virus vaccine given at the start of corticosteroid therapy in children with asthma.
A case-control study determined that the varicella vaccine had a protective efficacy of 86%. In addition, while varicella was moderate or severe in 37% of unvaccinated individuals who acquired this infection, no cases of moderate or severe infection occurred among the vaccinated. (Abstract 78.)
Retrospective evaluation of a varicella outbreak in a child care center determined that prior vaccination was associated with a protective efficacy of 84.4% and that all four children who developed severe varicella, including one with cerebellar ataxia, were unvaccinated. (Abstract 79.)
Arithromycin, given daily for five days, was successful in eradication of S. pyogenes from the oropharynx of both symptomatic (9 of 10) and also asymptomatic (139 (95%) of 147) children. Nasopharyngeal carriage of Streptococcus pneumoniae was also decreased from 43% to 115 (P < 0.001) but with an increase in proportion of erythromycin-resistant isolates from 5% to 35%. (Abstract 570.)
The prevalence of antibiotic resistance in S. pneumoniae continues to increase. One thousand seven hundred and three S. pneumoniae isolates from 2010 patients with pneumococcal pneumonia in 1997 in seven states were examined by broth microdilution antibiotic susceptibility testing; 9.1% were intermediate and 12.0% were resistant to penicillin. The proportion of isolates with a high level of penicillin resistance (MIC > 4 mcg/mL) increased from 3.5% in 1995 to 6.9% in 1997. Of the penicillin-resistant isolates, 36.8% were resistant to cefotaxime, 59.8% were resistant to erythromycin, and 96.0% were resistant to trimethoprim-sulfamethoxazole. (Abstract 51.)
A nationwide survey of susceptibility of 1476 strains of S. pneumoniae (17.9% pen-intermediate, 32.5% pen-resistant) and 1676 strains of H. influenzae (41.6% BL+) to seven orally administered beta-lactam and two macrolide antibiotics compared results using NCCLS MIC guidelines and pharmacodynamic (PD) MICs. The latter are based upon the necessity for the concentration of these antibiotics to remain above the MIC of an organism for 40-50% of the dosing interval to achieve efficacy. Although approximately 36% of S. pneumoniae are resistant to amoxicillin (and amoxicillin-clavulanate) by NCCLS standards, only approximately 6% are resistant by PD standards. (Abstract 195.) While 41% of penicillin-intermediate strains are resistant by NCCLS standard, fewer than 1% are resistant to this drug by PD criteria; 24% of penicillin-resistant strains are resistant by the latter criteria. Based on PD breakpoints, 99% of H. influenzae and 70% of S. pneumoniae were resistant to clarithromycin and azithromycin. By PD criteria, 88% of S. pneumoniae and 98% of H. influenzae were resistant to cefaclor. Cefixime, cefprozil, cefuroxime, and loracarbef perform only marginally better. (Abstract 195.)
The mechanisms of resistance of 109 strains of erythromycin-resistant S. pneumoniae collected from 30 U.S. centers were examined using a PCR technique designed to detect the methylase genes (ermAM, A, and C) and the macrolide efflux pump gene (mefA/E). One or the other was detected in 106 (97%) isolates; 66% contained mefA/E, while 34% contained ermAM. The MIC90 of the former (i.e., the efflux strains) was 4 mcg/mL, while for the latter (the methylase strains), it was more than 128 mcg/mL. (Abstract 225.) It is argued that clarithromycin may be effective in the treatment of strains with efflux (mefA/E) resistance since the concentration of the drug in epithelial lining cells and alveolar cells is at least 10 times higher than the MIC90 for these strains. (Abstract 264.)
The annual incidence of invasive pneumococcal infection in Baltimore was 17.8 per 100,000 population among whites and 59.2 per 100,000 among blacks (P < 0.01). The median age of blacks with infection was 27 years younger than whites, with most cases in the former occurring before the age of 65 years. (Abstract 182.) This observation has important implications with regard to strategies for immunization against pneumococcal infection.
Risk factors for the recovery of penicillin-resistant S. pneumoniae in veterans were "nosocomiality" and use of both systemic and inhaled corticosteroids. (Abstract 179.)
Four hundred fourteen subjects, including employees, students, and dependents, presenting to a college health service with a cough of more than six days duration seen over a 16-month period underwent microbiologic testing. Also screened were 77 asymptomatic contacts of someone with pertussis or individuals who had coughed for less than seven days. The mean duration of cough was 18 days for students and 24.4 days for nonstudents. An etiologic diagnosis was made in 76 (15%) of the total of 491 individuals; 4% of subjects had B. pertussis, 6% had RSV, 11% had M. pneumoniae, and 4% had C. pneumoniae infection. (Abstract 575.)
A five-component acellular pertussis vaccine (Pasteur Meriuex Connaught) was safe and immunogenic in adults and adolescents and could be combined with dT. (Abstract 80.)
Studies in nonsmoking volunteers found that the concentration of levofloxacin in epithelial lining fluid after a single oral dose of 500 mg was 9.9 mcg/mL at four hours, 6.5 mcg/mL at 12 hours, and 0.70 mcg/mL at 24 hours; results after a 750 mg dose were 50-100% greater. The epithelial lining fluid concentrations after a 500 mg dose of ciprofloxacin were, at the same sampling times, 1.9 mcg/mL, 0.4 mcg/mL, and undetectable. The concentrations of levofloxacin in alveolar macrophages four, 12, and 24 hours after a 500 mg dose of levofloxacin were 98 mcg/mL, 37 mcg/mL, and 14 mcg/mL, respectively; similar results were observed after a 750 mg dose. The results after a 500 mg dose of ciprofloxacin were 35 mcg/mL, 7 mcg/mL, and 2 mcg/mL. (Abstract 251.)
Levofloxacin use may cause a false-positive urine screen for opiates by the EMIT II assay. (Abstract 522.) Seventy-seven patients with moderate-to-severe community-acquired pneumonia were randomized to receive either ceftriaxone plus azithromycin or levofloxacin alone; successful outcomes were achieved in 89% and 93%, respectively. Treatment with levofloxacin was better tolerated. (Abstract 166.)
Levofloxacin therapy resulted in cure of 24 (92.3%) of 26 patients with Legionella pneumonia. The diagnosis had been made, in most cases, serologically, and 17 patients had evidence of infection with at least one additional pathogen. (Abstract 167.) A high success rate was also achieved in 128 patients with either M. pneumoniae or C. pneumoniae infection treated with levofloxacin. (Abstract 168.)
A case-control study compared 32 municipalities with prior outbreaks of Legionnaire's disease associated with potable water to 48 control municipalities. Hospitals using chlorinated water were 10.2 times more likely to have a reported outbreak of potable water-related Legionnaire's disease than were those receiving monochloramine-containing water (adjusted odds ratio 10.2; 95% CI 1.4 to 460). The authors conclude that 90% of such outbreaks, as well as many other community acquired cases, could be prevented by the use of monochloramine in hospital and municipal water supplies. (Abstract 574.) This study is provocative, but the results ultimately depend upon the detection of outbreaks, which, in turn, depends upon the sophistication of the local public health department.
Patients with "simple" pneumonia were automatically switched from IV antibiotic therapy to orally administered cefuroxime axetil when they had been afebrile for 48 hours, their WBC and band count were normalizing, and they were taking po medications. When compared to control patients, automatic switching was associated with decreased antibiotic costs, decreased overall costs and shortened length of stay (by 2.7 days; P = 0.0119). There was no difference in mortality. (Abstract 663.)
A retrospective analysis of data from two clinical trials found that there was no difference in cure rate of community-acquired pneumonia in veterans who received cefuroxime IV for 5-10 days (89.2%) compared to those treated with IV cefuroxime for two days followed by oral administration of cefuroxime axetil (89.4%). There was also no difference in cure rates between those receiving a total of seven days and those receiving a total of 10 days of antibiotic therapy. (Abstract 165.)
Fifty consecutive patients with severe lower respiratory tract infection were treated with cefepime while an additional 50 were given ceftazidime. Cure or improvement was achieved in 76% of cefepime and 66% of ceftazidime recipients (P = NS). The duration of post treatment hospitalization was significantly less in the cefepime cohort and the need for vancomycin use was also less (48% vs 80%; P = 0.001). (Abstract 170.)
Five hundred thirty-nine patients with nosocomial pneumonia were enrolled in two multicenter, blinded, randomized trials comparing trovafloxacin (initial dose given as IV alatrofloxacin) to either IV ciprofloxacin or IV ceftazidime, both followed by orally administered ciprofloxacin. Patients in the non-trovafloxacin comparator arms could also receive metronidazole or clindamycin for suspected anaerobic infections; patients in any of the three treatment groups could also receive additional anti-pseudomonal therapy or vancomycin for MRSA. The clinical success rate at the end of therapy was 76% in the trovafloxacin recipients and 74% for the combined comparator arms. (Abstract 169.)
Sixty ICU patients with pulmonary infiltrates with clinical pulmonary infection (CPI) scores less than 6 (indicating that, although pneumonia was considered unlikely but withholding antibiotics was undesirable) were randomized to receive ciprofloxacin for a "standard" duration or for 72 hours, at which time the need for continuation was evaluated. Antibiotic therapy was discontinued in the latter group if the CPI score remained less than 6 and no evidence of extrapulmonary infection was detected. Antibiotic therapy was continued in 29 (97%) of 30 assigned standard duration therapy and 11 (37%) of 30 assigned to 72-hour evaluation. Patient outcome in the two groups was similar, except for a greater proportion with superinfection in the standard duration arm (37%) compared to the short duration arm (17%). (Abstract 86.)
Musculoskeletal Infections
A retrospective review of 34 patients with osteomyelitis due to methicillin-susceptible S. aureus found that 25 had been treated with ceftriaxone (2 g q 24 h), seven with cefazolin, and two with vancomycin. The MIC of all isolates to ceftriaxone was less than 2.0 mcg/mL. All patients were treated for at least six weeks and followed for at least six months. Of the ceftriaxone-treated patients, 17 (68%) were cured, three were failures (all 3 had chronic osteomyelitis "not amenable to surgical debridement"), and five could not be assessed. Of those who received other treatment, one vancomycin recipient with retained infected hardware was a failure and the outcome in one could not be assessed. (Abstract 132.)
A retrospective study of patients with prosthetic joint infections (17 hip and 18 knee) due to Enterococcus species found that the median time from joint arthroplasty to evidence of infection was 370 days (range, 37-5106 days). A variety of approaches to management were taken—most of which were successful. The authors conclude that, "Following removal of a prosthesis with or without two-stage arthroplasty, monotherapy with a penicillin or vancomycin was as effective as combination therapy and combination therapy was associated with a high frequency of nephrotoxicity or ototoxicity." (Abstract 129.)
Endocarditis
Risk factors for mortality in patients with S. aureus endocarditis were APACHE III score more than 50, the occurrence of breakthrough bacteremia, being a transplant recipient, and EKG suggestive of endocarditis and methicillin-resistance. (Abstract 186.)
Central Nervous System Infection
The incidence of meningococcal infection in Maryland college students was similar to that in those of the same age in the general population, however, the incidence in college students residing in dormitories was three times greater. (Abstract 123.)
An apparently new endemic focus of LaCrosse virus was identified in eastern Tennessee. (Abstract 20.)
Sexually Transmitted Diseases
Famciclovir (250 mg bid), when compared to placebo, significantly reduced the frequency of recurrences of genital herpes as well as the frequency of asymptomatic viral shedding. The median time to the first clinically confirmed lesional episode was more than one year in those receiving famciclovir and only two months in placebo recipients (P = 0.0001). Famciclovir recipients experienced approximately 80% fewer episodes per year than did placebo recipients. The drug also reduced the frequency of shedding of the virus, both in the presence and absence of symptomatic recurrences. (Abstract 278.)
Five hundred mg famciclovir bid was effective in suppressing genital HSV recurrences in HIV-infected patients. (Abstract 406.)
Transplantation-Associated Infections
The detection of more than 100 copies of CMV DNA per mL of plasma had positive and negative predictive values, respectively, of 80% and 90% in the identification of patients at risk for CMV disease prior to bone marrow engraftment. (Abstract 61.)
Febrile Neutropenia
Patients with low-risk febrile neutropenia (expected duration of ANC < 500 for < 10 days and absence of organ system abnormality or hypotension) were randomized to receive, in a hospital setting, either ciprofloxacin 750 mg q 8 h plus amoxicillin-clavulanate 500 mg q 8 h (both given orally), or ceftazidime given q 8 h IV. This study of 280 episodes was blinded and placebo-controlled. Success without modification occurred in 72% of oral and 67% of IV episodes; there were no deaths. (Abstract 93.)
Prolonged Perplexing Pyrexia
In a retrospective analysis of 19 children with FUO with no diagnosis after inpatient evaluation, fever subsequently resolved in 16, two developed juvenile rheumatoid arthritis, and one had repeated bouts of intussusception. The mean follow-up was 3.5 years. (Abstract 69.)
Protozoan Infections
The sensitivity of direct visualization of aspiration and or touch-preparations in the diagnosis of cutaneous leishmaniasis was 48% while that of culture was 70% and histopathological examination was 76%. Detection by immunofluorescent antibody (IFA) in tissue had a sensitivity of 77% and specificity of 92%; the respective values for serum IFA were only 62% and 79%. PCR had a sensitivity of 91% and specificity of 85%. (Abstract 25.)
Two of 30 Greek patients with visceral leishmaniasis caused by L. infantum, treated with meglumine antimonate for 30 days failed to respond and two had severe drug reactions, while no failures or severe drug reactions were observed among 22 patients given liposomal amphotericin B for five days. No relapses were noted during 6-24 months of follow-up in either group. (Abstract 26.)
Eighty-four patients who had failed antimonial therapy for visceral leishmaniasis were treated with one of three doses of liposomal amphotericin B for five consecutive days. When evaluated two weeks after the completion of therapy, 27 (93%) of those receiving 0.75 mg/kg/d, 26 (93%) of those receiving 7.5 mg/kg/d, and 17 (100%) of those receiving 15 mg/kg/d were cured. (Abstract 270.)
The seroprevalence of infection with Trypanosoma cruzii in Mexico is reported to be only 0.2%. However, 14 (7.8%) of 179 patients with congestive cardiomyopathy in western Mexico (Jalisco, Zacatecas, and Mexico states) were believed to have Chagas disease as the etiology. Two were believed to be acutely infected—one was a 9-month-old infant believed to have been infected by transfusion. (Abstract 273.)
An explosive outbreak of chloroquine-resistant P. falciparum malaria occurred in an area bordering Yemen in southern Saudi Arabia, a country until recently believed to be largely free of this problem. (Abstract 29.) The first locally acquired chloroquine-resistant P. falciparum infections were reported in 1997 (Am J Trop Med Hyg 1997;56:573-575).
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