Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial Candida glabrata isolates.

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission, or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo.

Simulation of Legionnaires' disease prospective spatiotemporal cluster detection, Allegheny County, Pennsylvania, USA.

Legionnaires' disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014-2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.

The potential economic value of screening hospital admissions for Clostridium difficile.

Asymptomatic Clostridium difficile carriage has a prevalence reported as high as 51-85 %; with up to 84 % of incident hospital-acquired infections linked to carriers. Accurately identifying carriers may limit the spread of Clostridium difficile. Since new technology adoption depends heavily on its economic value, we developed an analytic simulation model to determine the cost-effectiveness screening hospital admissions for Clostridium difficile from the hospital and third party payer perspectives. Isolation precautions were applied to patients testing positive, preventing transmission. Sensitivity analyses varied Clostridium difficile colonization rate, infection probability among secondary cases, contact isolation compliance, and screening cost. Screening was cost-effective (i.e., incremental cost-effectiveness ratio [ICER] ≤ $50,000/QALY) for every scenario tested; all ICER values were ≤ $256/QALY. Screening was economically dominant (i.e., saved costs and provided health benefits) with a ≥10.3 % colonization rate and ≥5.88 % infection probability when contact isolation compliance was ≥25 % (hospital perspective). Under some conditions screening led to cost savings per case averted (range, $53-272). Clostridium difficile screening, coupled with isolation precautions, may be a cost-effective intervention to hospitals and third party payers, based on prevalence. Limiting Clostridium difficile transmission can reduce the number of infections, thereby reducing its economic burden to the healthcare system.

Performance of nested RT-PCR on CSF for tuberculous meningitis diagnosis in HIV-infected patients.

SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.

Detection of katG and inhA mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis.

BACKGROUND: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE: To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique. DESIGN: Descriptive study of 311 isolates from Ribeirão Preto, São Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType(®) MTBDRplus. RESULTS: katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223). CONCLUSION: INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH.

Invasive pneumococcal infection in Baltimore, Md: implications for immunization policy.

BACKGROUND: Streptococcus pneumoniae is a leading cause of infectious morbidity and mortality. Although blacks are known to have a higher incidence of invasive pneumococcal infection than whites, detailed analyses of these differences and their implications for vaccine prevention have not been reported. OBJECTIVE: To describe the epidemiological characteristics of invasive pneumococcal infection in Baltimore, Md, and its implications for immunization policy. METHODS: Analysis of active, laboratory-based surveillance during 1995 and 1996 among residents of the Baltimore metropolitan area. RESULTS: Of 1412 cases, 615 patients (43.6%) were classified as white and 766 (54.2%) as black. The annual incidence of invasive pneumococcal infection among white and black residents of the Baltimore metropolitan area was 17.8 and 59.2 per 100000 population, respectively (P<.01). Among patients aged 18 years and older, the median age of blacks with invasive pneumococcal infections was 27 years younger than that of whites (P<.01). Among males 40 to 49 years old, blacks had a 12-fold higher average incidence than whites (average incidence, 114.5 and 9.3, respectively; P<.01). By the age of 65 years, 83.8% of cases had occurred in black adults, as compared with 43.8% in white adults (P<.01). In a regression model, age, black race, male sex, low median family income, and county prevalence of acquired immunodeficiency syndrome were each independently associated with a higher incidence of pneumococcal infection. CONCLUSIONS: Young urban black adults in the Baltimore metropolitan area have a dramatically higher incidence of invasive pneumococcal infection than whites. The vast majority of cases of invasive pneumococcal infection in blacks occur before age 65 years. Current immunization efforts have not addressed the high incidence of pneumococcal infection in this population.

A cluster of meningococcal disease on a school bus following epidemic influenza.

An outbreak of meningococcal disease among children on a school bus offered the opportunity to study a proposed association between this infection and preceding influenza infection. Five students who rode the bus became ill with invasive group C meningococcus. Transmission was limited to the bus; there was no evidence for school transmission. All five students reported influenza-like symptoms within several weeks before the development of meningococcal disease. School absenteeism, principally due to upper respiratory tract illness, was higher during the 3 weeks before the outbreak of meningococcal disease than during any period in the preceding 3 1/2 years, suggesting an unusually severe outbreak of respiratory illness. A case-control study comparing students with and without influenza symptoms revealed that the outbreak of respiratory disease was due to B/Ann Arbor/1/86 influenza (geometric mean titers, 86 for 80 patients and 33 for 47 controls [P = .0007]). These data add to the evidence suggesting that influenza respiratory infection predisposes to meningococcal disease.

Protease inhibitors as initial therapy for individuals with an intermediate risk of HIV disease progression: is more necessarily better?

OBJECTIVE: To compare three possible therapeutic strategies for the treatment of patients with an intermediate risk of HIV disease progression. DESIGN: Mathematical modeling based on assumptions derived from published data. METHODS: A parametric survival model was fitted to empirical data to describe the survival trajectory of untreated individuals. It was assumed that successful treatment decreases the risk of disease progression curing the first year after its introduction by a constant that is dependent on the magnitude of the initial drop in HIV viral load. Thereafter, individual members of the treatment cohort follow different pathways, depending on the duration of the initial response or, in case of virologic failure, the response to a new drug regimen. RESULTS: Sub-groups of patients starting therapy with two nucleoside reverse transcriptase inhibitors (NRTI) or two NRTI and a protease inhibitor had the highest instantaneous risk of disease progression at the end of the 5-year follow-up period. Patients who started therapy with two NRTI and a non-NRTI had the lowest likelihood of progression to AIDS or death at 5 years of follow-up. This is because, in the case of the subgroup whose initial treatment included a protease inhibitor, failure rates due to non-adherence to therapy are high and response to salvage therapy is limited by past protease inhibitor experience. CONCLUSIONS: Despite the superior virologic potency of the protease inhibitor-containing regimens, in this analysis other strategies performed equally well or even better. In the absence of solid empirical data and until the advent of antiretroviral regimens that are shown to be safe, simple to take, and maximally suppress viral load, caution may be required in selecting the long-term therapy for patients with less advanced HIV disease.

Chemoprophylaxis for tuberculosis and survival of HIV-infected patients in Brazil.

OBJECTIVE: To study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test. DESIGN: Prospective observational cohort study. SETTING: Outpatient clinic of a university hospital, in Rio de Janeiro, Brazil. PATIENTS: Two-hundred and ninety-seven patients with a positive tuberculin skin test (reaction > or = 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998. INTERVENTION: The use of chemoprophylaxis for tuberculosis. MAIN OUTCOME MEASURES: Death was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses. RESULTS: The median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14-1.04; P = 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09-0.65; P = 0.002). CONCLUSIONS: Anti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence of Mycobacterium tuberculosis infection.

Risk factors for HIV-2 infection in Guinea-Bissau.

To define the epidemiology of HIV-2 infection, we conducted a case-control study among hospitalized patients at an acute care hospital in Bissau, Guinea-Bissau, a country with endemic HIV-2 infection. Among 128 patients with various diagnoses, 23 (18%) were positive for HIV-2 by ELISA and Western blot. One of these patients was serologically reactive for HIV-1 also, but PCR and viral culture revealed the presence of HIV-2 only. To study risk factors, behaviors, and AIDS knowledge related to the acquisition of HIV infection, 22 HIV-2-seropositive and 21 seronegative hospitalized patients were given a physical examination and administered a questionnaire. Among women, transfusion was associated with HIV-2 infection (OR = 14.4, p = 0.02); among men, sex with a prostitute was the principal risk factor (OR = undefined, p = 0.02). Although 79% of HIV-infected patients and controls had heard of AIDS, only 17% of all study participants and 50% of males reporting sex with prostitutes had used condoms in the previous year. These data suggest that the risk factors for HIV-2 infection are similar to those for HIV-1 and support previous studies showing that HIV-2 is the predominant HIV in Guinea-Bissau. Efforts to decrease transmission of HIV-2 should include screening for HIV-2 in blood for transfusion in endemic areas (now done in Bissau) and education about the risk of sexual transmission.

Myelopathy among Brazilians coinfected with human T-cell lymphotropic virus type I and HIV.

OBJECTIVE: To determine whether subjects coinfected with HTLV-I and HIV have a higher frequency of myelopathy than subjects singly infected with HIV. DESIGN: A prospective, nested case-control study of HTLV-I and HIV coinfected (cases) and HIV singly infected adults (controls) participating in a prospective HIV cohort study at a university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. MEASUREMENTS: Subjects were evaluated for evidence of myelopathy by a neurologist unaware of their HTLV serologic status. Patients with at least two pyramidal signs, such as paresis, hypertonicity or spasticity, hyperreflexia, clonus, diminished or absent superficial reflexes, or the presence of pathologic reflexes (e.g., Babinski or Hoffmann), were defined as having myelopathy. Myelopathy severity was quantified using the Kurtzke Functional Disability Scale (FDS); patients with FDS scores > or = 4 were considered to have significant myelopathy. Selected patients with myelopathy underwent lumbar puncture for the evaluation of intrathecal synthesis of HTLV-I antibodies. RESULTS: Of 15 coinfected subjects, 11 (73%) had evidence of myelopathy versus 10 of 62 subjects (16%) with HIV single infection (adjusted odds ratio [OR] = 13.0, p = 0.00002). When only myelopathy patients with FDS scores of > or = 2 or > or = 4 were included, the association between coinfection and the presence of myelopathy remained (OR = 7.3, p = 0.0003 for scores > or = 2; and OR = 8.9 for scores > or = 4, p = 0.04). In addition, a higher proportion of coinfected subjects had peripheral neuropathy (40%) than controls (16%) (OR = 3.5, p = 0.07). CONCLUSION: Coinfection with HTLV-I was strongly associated with myelopathy among subjects infected with HIV. The relative contribution of HTLV-I versus HIV in the pathogenesis of coinfection-associated myelopathy is not known. Coinfection may also be associated with peripheral neuropathy. Further studies are needed to elucidate the mechanisms of coinfection-associated neurologic conditions.

Haemophilus influenzae type b polysaccharide vaccine: an efficacy study. Haemophilus Vaccine Efficacy Study Group.

The Haemophilus influenzae type b polysaccharide vaccine was licensed for use in the United States in April 1985. Postlicensure case-control efficacy studies have yielded markedly different estimates of efficacy, leading to contradictory recommendations to practicing physicians. To obtain additional information about the efficacy of the vaccine, we studied cases of invasive Haemophilus influenzae type b disease ascertained through active surveillance in areas with a total population of 34 million. We enrolled children 24 to 59 months of age who did not attend day-care centers. (Data from our day-care study have been published elsewhere.) For each case child, as many as three 24- to 59-month-old control children were chosen from a roster of acquaintances supplied by the child's parent. Conditional logistic regression was used, and vaccine efficacy was estimated to be 62% (95% confidence interval = 0%, 85%), which did not change significantly after adjusting for age and parental smoking, variables that were significantly different for case and control children. Results of this study support our previous finding of a positive protective efficacy, albeit lower than the efficacy of 90% found in children 18 to 71 months of age in the Finnish prelicensure trial.

HIV disease progression and V3 serotypes in Brazil: is B different from B-Br?

HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.

Experimental coronary artery fistula.

Despite numerous clinical reports of coronary artery fistulas, there have been no laboratory models. A circumflex coronary-pulmonary artery fistula was constructed with a vein graft in 11 adult foxhounds. A temporary intravascular shunt obviated the need for cardiopulmonary bypass. Measurements of aortic flow, arterial pressure, left ventricular pressure and its derivative, heart rate, and flow in the proximal coronary, distal coronary, and fistula were made with the fistula open and closed in 9 animals. Mean fistula flow was 89 c.c. per minute, representing a 1.1:1 left-to-right shunt. Mean proximal coronary flow increased 211 per cent, and there was a relative steal of 26 per cent of distal coronary flow with the fistula functioning. Phasic flow patterns showed continuous systolic and diastolic flow in the proximal coronary artery and fistula. Despite the striking changes in coronary flow patterns, there was no significant effect on measured left ventricular function. Futher uses for this model and variations of it aresuggested.

Extraction of intramyocardial foreign body utilizing operative ultrasonography.

Technical advances in cardiac surgery have made accessible previously remote regions within the heart and great vessels; nevertheless, limitations in the ability to locate intramyocardial foreign bodies with precision utilizing conventional radiographic techniques, together with the frequent inability to palpate a foreign body located within the walls of the heart chambers, has dampened early enthusiasm for their removal. Despite this, the recognized complications associated with nonoperative management continue to militate for an aggressive approach. The following case illustrates the use of operative high-frequency ultrasonography in the exact localization of an intramyocardial foreign body. The precision thus afforded minimizes operative time, confines the size of the necessary ventriculotomy, and greatly facilitates successful removal.

Vasoactive intestinal polypeptide in cardiac myxoma.

A case of left atrial myxoma is reported in which tumor tissue was found to contain high levels of vasoactive intestinal polypeptide. This finding further supports the concept that myxomas are true neoplasms and may explain some of the poorly understood clinical manifestations of this tumor.

Comparative efficacy of oral rifampin and topical chloramphenicol in eradicating conjunctival carriage of Haemophilus influenzae biogroup aegyptius. Brazilian Purpuric Fever Study Group.

Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented. Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil. Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF. During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H. influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis. Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later. At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01). Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF.

Caretaker recognition of respiratory signs in children: correlation with physical examination findings, x-ray diagnosis and pulse oximetry.

Caretaker recognition of clinical utility of respiratory signs and symptoms in the prediction of pneumonia was examined in a prospective study of infants and children in four cities in Egypt. In all 688 children aged 2 months-5 years presenting with a history and/or physical examination findings of cough and difficult or fast breathing were recruited from out-patient health facilities. The validity of caretaker terms was determined using paediatrician observation of standard respiratory signs and symptoms, x-ray diagnosis and pulse oximetry as standards. The sensitivity of 'nahagan' (Egyptian Arabic for fast breathing) for identifying elevated respiratory rate was 78% +/- 4, and was slightly higher for < 12 month olds (85% +/- 5) versus children aged 1-5 years (74% +/- 5). 'Sedro tale nazel', which describes the chest as moving up and down, was a sensitive (86% +/- 3) and specific (60% +/- 4) indicator of chest indrawing. 'Tazyeek' (wheeze) had a sensitivity of 75% +/- 3 and specificity of 66% +/- 4 when compared to paediatrician assessment of wheezing during physical examination. Although not specific, the caretaker terms, 'nahagan' or 'nafas seria' (fast breathing) and 'sedro tale nazel' (chest indrawing), either spontaneously or after asking, were sensitive (> 71%) indicators of radiologic pneumonia and oxygen desaturation, and therefore can be used to prompt timely health seeking behaviour in these settings.

Maternal reporting of acute respiratory infection in Egypt.

BACKGROUND: Acute respiratory infection (ARI) is a major cause of childhood morbidity and mortality in developing countries. Community surveys are used to determine the proportion of children with ARI for whom care is sought by questioning mothers about the signs and symptoms of illness episodes. The validity of this approach has been studied infrequently. METHODS: We evaluated maternal reporting of signs and symptoms 2 and 4 weeks after diagnosis among 271 Egyptian children < 5 years old. Children with ARI were evaluated by physical examination, chest radiography, and pulse oximetry, and were alternately assigned for a maternal interview about the episode 14 or 28 days later. RESULTS: For radiographically-defined acute lower respiratory infection (ALRI), the sensitivity of several symptoms for combined open- and close-ended questions was relatively high: nahagan (deep or rapid breathing) (80%), nafas sarie (fast breathing) (66%), and kharfasha (coarse breath sounds) (63%). The specificity of these terms was 50-68%. The specificity was inversely related to the follow-up time. No term provided both a sensitivity and specificity of > 50% at day 28 across the radiographically, clinically- and pulse oximetry-based definitions of ALRI. Spontaneously mentioned karshet nafas (difficult or rapid breathing) at 14 days had a specificity and sensitivity for radiographic ALRI of 87% and 41%, respectively, suggesting that this term is a good choice for community surveys. CONCLUSIONS: Maternal reporting of ARI symptoms is non-specific 2 and 4 weeks after diagnosis but may be useful for monitoring trends in the proportion of children with pneumonia who receive medical care. To maximize specificity, ARI programmes should generally use a recall period of 2 weeks.

PIP: Acute respiratory infection (ARI) is a major cause of childhood morbidity and mortality in developing countries. Community surveys are used to determine the proportion of children with ARI for whom care is sought by questioning mothers about the signs and symptoms of illness episodes. The validity of this approach has been studied infrequently. Maternal reporting of signs and symptoms was evaluated 2 and 4 weeks after diagnosis among 271 Egyptian children 5 years old selected from a prospective study of the signs and symptoms of pneumonia in Ismailia and Assiut. Children with ARI were evaluated by physical examination, chest radiography, and pulse oximetry, and were alternately assigned for a maternal interview about the episode 14 or 28 days later. Nahagan (deep or rapid breathing), yenet (grunting), and karshet nafas (difficult or rapid breathing) were the most frequently mentioned terms reported by 49%, 28%, and 31% of the mothers, respectively. For radiographically-defined acute lower respiratory infection (ALRI), the sensitivity of several symptoms for combined open- and close-ended questions was relatively high: nahagan (80%), nafas sarie (fast breathing) (66%), and kharfasha (coarse breath sounds) (63%). The specificity of these terms was 50-68%. In general, the sensitivity was greater for 14- or 28-day recall than day 0, but the specificity was inversely related to the follow-up time. No term provided both a sensitivity and specificity of 50% at day 28 across the radiographically, clinically- and pulse oximetry-based definitions of ALRI. Spontaneously mentioned karshet nafas (difficult or rapid breathing) at 14 days had a specificity and sensitivity for radiographic ALRI of 87% and 41%, respectively, suggesting that this term is a good choice for community surveys. Maternal reporting of ARI symptoms is non-specific 2 and 4 weeks after diagnosis but may be useful for monitoring trends in the proportion of children with pneumonia who receive medical care. To maximize specificity, ARI programs should generally use a recall period of 2 weeks.