Investigation and management of chronic cough using a probability-based algorithm.

Chronic cough is a common and distressing symptom. A novel algorithm has been developed for the management of chronic cough, in which an assessment of clinical probability of disease determines the need to proceed to investigation. In this study, the performance of this algorithm in clinical practice was prospectively evaluated. A total of 131 consecutively referred patients (86 females) whose principal presenting symptom was a cough of duration >8 weeks were studied. Their age (median (range)) was 60 (16-88) yrs and cough duration 5.9 (0.2-65) yrs. A cause of cough was established in 93% of cases. The most frequent diagnoses were asthma (24% of cases), gastro-oesophageal disease (22%), post-viral cough (8%), bronchiectasis (8%) and interstitial lung disease (8%). Primary pulmonary disease was significantly more likely in patients with a productive cough and in patients with an abnormal chest radiograph. Only a small proportion (<8%) of patients had multiple causes of cough. The probability of treatment started on the basis of a high clinical suspicion of either asthma, gastro-oesophageal disease or rhinitis being successful was 74%. Overall, 26% of the patients were managed successfully without the need for any form of investigation other than chest radiography and spirometry. Use of the algorithm resulted in identification of the cause of cough and successful treatment in the large majority of cases. It is concluded that this protocol has the potential to improve management by providing a structured approach, reducing the number of investigations performed, and minimising unnecessary delays in treatment.

Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis.

BACKGROUND: It has been proposed that the pH of airway lining fluid may regulate the fractional exhaled concentration of nitric oxide (Fe(NO)) in respiratory disease. METHODS: Fe(NO), exhaled breath condensate (EBC) pH, and EBC concentrations of nitrite plus nitrate (NO2/NO3) were compared in 12 subjects with stable asthma, 18 with stable cystic fibrosis (CF), and 15 healthy control subjects. Eight of the CF patients were studied on a separate occasion at the start of a pulmonary exacerbation. RESULTS: Fe(NO) was significantly greater in asthmatic subjects than in control subjects (mean 35 v 9 ppb, p<0.001). EBC pH, however, was similar in the asthmatic and control groups (median 5.82 v 6.08, p=0.23). Levels of NO2/NO3 were on average higher in EBC samples from asthmatic subjects, but the difference was not significant. In patients with stable CF both the Fe(NO) (mean 4 ppb, p<0.001) and EBC pH (median 5.77, p=0.003) were lower than in the control group. Levels of EBC NO2/NO3 (median 29.9 microM; p=0.002) in patients with stable CF, in contrast, were significantly higher than in control subjects. During CF exacerbations, EBC pH was further reduced (median 5.30, p=0.017) but Fe(NO) and NO2/NO3 were unchanged. CONCLUSIONS: These findings demonstrate a dissociation between EBC pH and Fe(NO) in inflammatory airways disease.

Patients' and carers' preferences in two models of care for acute exacerbations of COPD: results of a randomised controlled trial.

BACKGROUND: Patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) were randomised to either hospital at home (HaH) or inpatient management, and patient and carer preferred site of management and satisfaction with care received in the two arms was determined. METHODS: Emergency admissions with an acute exacerbation of COPD were randomised to inpatient care or HaH care. After discharge an independent observer administered a questionnaire to both patients and carers on the preferred site of care and scored satisfaction with the care received. RESULTS: Of 60 patients recruited, 30 were randomised to receive HaH care. Retrospective patient preference for HaH care was 96.3% in the domiciliary arm and 59.3% in the conventional arm; carer preference figures were 85.7% and 42.9%, respectively. There was a higher preference for domiciliary care by both patients and carers in the HaH arm than in the inpatient arm (p=0.001 and p=0.01, respectively). Patients recorded equal satisfaction with care in the two arms (88.1% in the conventional arm, 91.7% in the domiciliary arm); carer scores were 91.3% and 91.9%, respectively. CONCLUSIONS: The results of this study show that both patients and carers were significantly more likely to prefer domiciliary care if they were in the HaH arm. Since patients had to be willing to be looked after at home, both patients' and carers' perceptions of the benefits of HaH care were reinforced by their experience. HaH care of acute exacerbations of COPD is the preferred option in suitable patients.

Recent transmission of tuberculosis in a cohort of HIV-1-infected female sex workers in Nairobi, Kenya.

OBJECTIVES: To describe the epidemiological and clinical characteristics of HIV-related tuberculosis in a female cohort, and to investigate the relative importance of recently transmitted infection and reactivation in the pathogenesis of adult HIV-related tuberculosis. DESIGN: Members of an established cohort of female sex workers in Nairobi were enrolled in a prospective study. Women were followed up regularly and seen on demand when sick. METHODS: Between October 1989 and September 1992 we followed 587 HIV-infected and 132 HIV-seronegative women. Standard protocols were used to investigate common presentations. Cases of tuberculosis were identified clinically or by culture. All available Mycobacterium tuberculosis strains underwent DNA fingerprint analysis. RESULTS: Forty-nine incident and four recurrent episodes of tuberculosis were seen in HIV-infected women; no disease was seen in seronegative sex workers (P = 0.0003). The overall incidence rate of tuberculosis was 34.5 per 1000 person-years amongst HIV-infected participants. In purified protein derivative (PPD) skin test-positive women the rate was 66.7 per 1000 person-years versus 18.1 per 1000 person-years in PPD-negative women. Twenty incident cases (41%) were clinically compatible with primary disease. DNA fingerprint analysis of strains from 32 incident cases identified two clusters comprising two and nine patients; allowing for index cases, 10 patients (28%) may have had recently transmitted disease. Three out of 10 (30%) patients who were initially PPD skin test-negative became PPD-positive. Taken together, 26 incident cases (53%) may have been recently infected. DNA fingerprint analysis also identified two (50%) of the four recurrent tuberculosis episodes as reinfection. CONCLUSIONS: Substantial recent transmission of tuberculosis appears to be occurring in Nairobi amongst HIV-infected sex workers. It may be incorrect to assume in other regions of high tuberculosis transmission that active HIV-related tuberculosis usually represents reactivation of latent infection.

PIP: A 3-year (1989-92) prospective study of 587 HIV-positive and 132 HIV-negative commercial sex workers in Nairobi, Kenya, revealed substantial recent transmission of tuberculosis in the HIV-infected group. The cohort was enrolled at a community clinic that provides counseling, sexually transmitted disease services, and free condoms. In HIV-positive women, 49 incident and 4 recurrent episodes of tuberculosis were diagnosed during the study period; there were no tuberculosis cases among HIV-negative women. The overall incidence rate of tuberculosis was 34.5/1000 person-years among HIV-positive women. 20 incident cases (41%) met the clinical case definition of primary disease. DNA fingerprint analysis of strains from 32 incident cases suggested 10 women (28%) may have had recently transmitted disease. 3 of 10 women who were initially purified protein derivative (PPD) skin test-negative became PPD-positive. Clinical presentation, tuberculin skin testing, and strain clustering data all independently suggested that substantial Mycobacterium tuberculosis transmission was occurring in HIV-infected prostitutes during the study period. As many as 26 (53%) of the 49 patients with incident disease may have recently acquired tuberculosis and DNA fingerprint analysis identified 2 (50%) of the 4 recurrent tuberculosis episodes as reinfection. These findings challenge the assumption that tuberculosis in HIV-infected individuals represents reactivation of latent endogenous infection.

Responsiveness of human immunodeficiency virus type 1-infected Kenyan women with or without prior pneumococcal disease to pneumococcal vaccine.

In East Africa, Streptococcus pneumoniae is a common and serious, but potentially preventable, human immunodeficiency virus type 1 (HIV-1)-associated pathogen. For 54 HIV-1-infected women, baseline levels of capsule-specific antibody to 2 of 4 pneumococcal serotypes were lower than levels in 15 seronegative women (P < .05). After immunization, specific antibody to all 4 serotypes increased in HIV-1-infected and -uninfected women (P < .05). Convalescent levels for 2 of 4 serotypes were greater in seronegative women, but the levels were not different between HIV-1-infected women with (n = 21) or without (n = 33) prior invasive pneumococcal disease. The baseline functional activity to kill S. pneumoniae type 14 was lower in HIV-1-infected than -uninfected women but also rose significantly in all groups after immunization. It is concluded that HIV-1 infection in Kenyan women is associated with decreased levels of natural antibody to selected pneumococcal capsular serotypes, but the vaccine is immunogenic in these patients who are at high risk of invasive pneumococcal disease.

No increased prevalence of adrenocortical insufficiency in human immunodeficiency virus-associated tuberculosis.

SETTING: Acute medical wards, Kenyatta National Hospital, Nairobi, Kenya. OBJECTIVE: To determine the prevalence of adrenocortical insufficiency in human immunodeficiency virus (HIV)-1 infected and non-infected patients with tuberculosis. DESIGN: One hundred and seventy-four patients with proven tuberculosis (90 HIV-1 positive and 84 HIV-1 negative) were assessed for adrenocortical insufficiency with a 30 min synacthen stimulation test. RESULTS: Fifty-one percent of those with pulmonary tuberculosis and 56% of those with extra-pulmonary tuberculosis had a subnormal cortisol response. However there was no statistically significant difference between the HIV-1 infected and non-infected patients in either group. CONCLUSION: While an impaired cortisol response is common in tuberculosis, it is no more prevalent in HIV-1 infected patients than non-infected patients with tuberculosis.

Bacteriuria in a cohort of predominantly HIV-1 seropositive female commercial sex workers in Nairobi, Kenya.

Although significant bacteriuria and urinary tract infection are more common in immunocompetent women than men, studies linking HIV immunosuppression with an increased risk of developing urinary infection have so far only been carried out in men. We therefore examined the relationship between bacteriuria and HIV status and CD4+cell count in a relatively homogeneous cohort of female commercial sex workers (CSW) attending a community clinic in Nairobi. Two hundred and twenty-two women were enrolled, and grouped according to HIV status and CD4 count. Group 1 were HIV seronegative (n = 52); Group 2 were HIV seropositive with CD4 + counts above 500 x 10(6)/l (n = 51); Group 3 were HIV seropositive with CD4 + counts between 201 and 500 x 10(6)/l (n = 67); Group 4 were HIV seropositive with CD4+counts below 200 x 10(6)/l (n = 52). Clinical signs and symptoms were noted and mid-stream specimens of urine obtained for culture and sensitivity. Overall 23% (50/222) had significant bacteriuria. The rates in each group respectively were 25%, 29%, 19% and 23% and there was no significant association between bacteriuria and HIV status; or between bacteriuria and level of immuno-suppression as indicated by CD4 + count. Overall 19% (30/222) of women had symptoms (frequency; dysuria; loin pain; smelly urine) or signs (fever; loin tenderness) compatible with urinary tract infection. However there was no significant association between symptoms or signs of infection and bacteriuria or HIV status. A typical range of pathogens, predominantly Enterobacteriaceae, were isolated and there were high rates of resistance to commonly used antimicrobials as well as 10% resistance to ciprofloxacin. Although high rates of significant bacteriuria can occur in highly sexually-active women, this appears unrelated to HIV infection or the level of HIV-related immunosuppression and is generally asymptomatic or clinically indistinct.

Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya.

BACKGROUND: HIV infection is a major risk factor for pneumococcal disease in industrialised countries. Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction. We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease. METHODS: A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992. 587 participants were HIV positive and 132 remained HIV negative. Set protocols were used to investigate common presentations. Cases were identified clinically and radiographically. Streptococcus pneumoniae and other pathogens were diagnosed by culture. FINDINGS: Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17.8, 95% CI 2.5 to 126.5). In seropositive women the incidence rate was 42.5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years. By serotyping, most recurrent events were re-infection. A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11%. Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae. At first presentation the mean CD4 cell count was 302/microL(SD 191) and was 171/microL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 0.29 to 0.66). Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae. INTERPRETATION: Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa.

Serological responses to brucellosis in HIV-seropositive patients.

Serial sera from 2 patients infected with the human immunodeficiency virus (HIV) type 1 attending a clinic in Nairobi, Kenya, and with blood cultures yielding Brucella melitensis, were tested by enzyme-linked immunosorbent assay for their serological response (Brucella-specific immunoglobulin (Ig) M and IgG) to Brucella infection. Antibody responses were comparable to those of immunocompetent individuals, one patient showing serology typical of acute brucellosis, the other of chronic brucellosis. Sera from 100 other patients, 65 of whom were HIV-positive, attending the same clinic but whose routine microbiological cultures were negative for Brucella, were tested retrospectively for Brucella-specific antibody. Eight had Brucella-specific IgM and IgG, 6 had IgM only and 21 had IgG only, suggesting relatively high levels of exposure to Brucella in the study cohort. There was no association between Brucella antibody status and HIV status. Brucellosis is probably underdiagnosed in Kenya. Brucella serology may be helpful in the diagnosis of patients with non-specific symptoms in East Africa, regardless of HIV status.

Nasopharyngeal carriage of Staphylococcus aureus and carriage of tetracycline-resistant strains associated with HIV-seropositivity.

The aim of this prospective study was to investigate the relationship between carriage of antibiotic-resistant Staphylococcus aureus and infection with the human immunodeficiency virus (HIV). A total of 554 pernasal swabs was taken during a six-month period from 554 adult patients attending three outpatient clinics and from inpatients from a hospital in Nairobi, Kenya. Overall, 121 swabs (22%) yielded Staphylococcus aureus, there being significantly higher carriage in HIV-positive patients (71/264, 27%) than in HIV-negative patients (50/290, 17%); p = 0.008. Antimicrobial resistance rates were determined for 110 isolates and were high for penicillin (91%) and tetracycline (72%) and low for erythromycin (8%), methicillin (3%), gentamicin (5%) and chloramphenicol (0%). Genetic analysis showed plasmids in the range of 24-42 MDa to be associated with beta-lactamase production and plasmids in the range of 3-5 MDa to be associated with resistance to tetracycline, erythromycin and trimethoprim. All nine erythromycin-resistant strains were from HIV-positive patients (p = 0.02). There was a significant association of tetracycline resistance with HIV seropositivity (p = 0.002). The association of HIV seropositivity with Staphylococcus aureus carriage and carriage of antibiotic-resistant strains against the background of the HIV epidemic are of relevance in individual patient care and raise concern for public health.

PIP: The authors report findings from a prospective study conducted to investigate the relationship between the carriage of antibiotic-resistant Staphylococcus aureus and infection with HIV. 554 pernasal swabs were taken during a six-month period from 554 adult patients attending three outpatient clinics and from inpatients in a hospital in Nairobi, Kenya. 22% of swabs yielded Staphylococcus aureus, with significantly higher carriage in HIV-positive patients than in HIV-negative patients: 27% and 17%, respectively. Antimicrobial resistance rates determined for 110 isolates were 91% for penicillin, 72% for tetracycline, 8% for erythromycin, 3% for methicillin, 5% for gentamicin, and 0% for chloramphenicol. Genetic analysis identified plasmids in the range of 24-42 MDa associated with B-lactamase production and plasmids in the range of 3-5 MDa associated with resistance to tetracycline, erythromycin, and trimethoprim. All nine erythromycin-resistant strains were from HIV-positive patients. There was a significant association of tetracycline resistance with HIV seropositivity.