Respiratory tract infection in HIV-1-infected adults in Nairobi, Kenya: evaluation of risk factors and the world health organization treatment algorithm.

To evaluate the WHO (World Health Organization) algorithm for management of respiratory tract infection (RTI) in HIV-1-infected adults and determine risk factors associated with RTI, we enrolled a cohort of 380 HIV-1-seropositive adults prospectively followed for incident RTI at an outpatient clinic in Nairobi, Kenya. RTI was diagnosed when patients presented with history of worsening or persistent cough. Patients were treated with ampicillin, or antituberculosis therapy when clinically indicated, as first-line therapy and with trimethoprim/sulfamethoxazole as second-line therapy. Five hundred ninety-seven episodes of RTI were diagnosed: 177 of pneumonia and 420 of bronchitis. The WHO RTI algorithm was used for 401 (95%) episodes of bronchitis and 151 (85%) episodes of pneumonia (p <.001). Three percent of bronchitis cases versus 32% of pneumonia cases failed to respond to first-or second-line treatment (p <.0001). Being widowed (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.0-4.4), less than 8 years of education (adjusted OR = 2.5, CI: 1.5 - 4.1), and CD4 count < 200 cells/microl (adjusted OR = 2.4, CI: 1.4-3.9) were risk factors for pneumonia. A high percentage of patients (32%) with pneumonia required a change in treatment from that recommended by the WHO guidelines. Randomized trials should be performed to determine more appropriate treatment strategies in HIV-1-infected individuals.

Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial.

OBJECTIVES: To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya. SUBJECTS: Six hundred and eighty-four HIV-1-infected adults. MAIN OUTCOME MEASURES: Development of tuberculosis and death. RESULTS: Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12). CONCLUSIONS: Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

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.

Microbiology of HIV associated bacteraemia and diarrhoea in adults from Nairobi, Kenya.

We undertook a retrospective descriptive comparison of the spectrum of pathogens responsible for bacteraemia and diarrhoea in HIV antibody positive and negative patients over 4 years (1988-92), in Nairobi, Kenya. The study population was recruited from primary to tertiary centres of clinical care and consisted of 2858 adults (15 years or older). There were 415 significant blood culture isolates, 192 from 1785 HIV negative patients and 223 from 953 HIV positive patients. There were 233 significant faecal isolates, 22 from 115 HIV negative patients and 211 from 531 HIV positive patients. The most common pathogens detected in blood were Streptococcus pneumoniae and Salmonella typhimurium and in faeces Shigella flexneri, S. typhimurium and Cryptosporidium parvum. The agents causing illness in HIV positive patients in Nairobi are similar to those prevalent in the HIV negative community and the investigation of a febrile illness with or without diarrhoea in an HIV positive patient should reflect this.

PIP: Researchers conducted a retrospective analysis of stool specimens from 646 adult patients and of blood cultures from 2738 adult patients to examine the etiology of opportunistic infection in HIV-positive individuals in Nairobi, Kenya, and to compare this etiology with the range of pathogens causing disease in the HIV-negative population. Adults at least 15 years old contributed the stool and blood samples that were received at the Wellcome Trust-Kenya Medical Research Institute during 1988-92. The 415 significant blood culture isolates comprised 192 from 1785 HIV-negative patients and 223 from 953 HIV-positive patients. The most frequently detected pathogens in blood included Streptococcus pneumoniae (58 in HIV-positive cases and 25 in HIV-negative cases) and Salmonella typhimurium (56 in HIV-positive cases; 5 in HIV-negative cases). There were 233 significant stool isolates, 211 from 531 HIV-positive patients and 22 from 115 HIV-negative patients. 20 blood cultures and 21 stool cultures had more than 1 significant pathogen. The most commonly detected organisms in the stools were Shigella flexneri (49 for HIV-positive cases and 9 in HIV-negative cases), S typhimurium (40 in HIV-positive cases and 3 in HIV-negative cases), and Cryptosporidium parvum (45 in HIV-positive cases and 0 in HIV-negative cases). With two exceptions, the spectrum of pathogens associated with infection in HIV-positive patients was the same as that for HIV-negative patients. Physicians should consider this when they investigate and manage febrile illness with or without diarrhea in an HIV-positive patient.

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.

Infection and morbidity in patients with tuberculosis in Nairobi, Kenya.

OBJECTIVE: To examine the role of acute infection as a cause of morbidity in patients with tuberculosis. DESIGN: Cross-sectional documentation of predefined acute morbid events. SETTING: Infectious Diseases Hospital, Nairobi, Kenya. PATIENTS: Adults (> or = 15 years), inpatients and outpatients with a diagnosis of tuberculosis presenting with one or more of a series of clinical features. A new event was defined as one occurring at least 1 week after the initial event. INTERVENTIONS: Patients' treatment was modified depending on the results of laboratory investigations. MAIN OUTCOME MEASURES: There were 642 events from 398 patients, 235 HIV-positive patients had 438 events and 163 HIV-negative patients had 204 events (P < 0.0001). Forty-two out of the 235 (18%) HIV-positive patients were bacteraemic compared with nine out of the 163 (6%) HIV-negative patients (P = 0.0003). The most common isolates from blood were Salmonella typhimurium and Streptococcus pneumoniae. RESULTS: Faecal specimens were obtained more commonly from HIV-positive patients (P < 0.001), and often contained bacterial pathogens. CONCLUSIONS: Many of the causes of morbidity in patients with tuberculosis and HIV are not due to tuberculosis or antituberculous therapy, and will not be identified without microbiological investigation.

PIP: Tuberculosis (TB) is a common complication of HIV in Africa. A 1988-89 study further confirmed that considerable morbidity and mortality from acute bacterial infection occurred in HIV patients. It has also been found that anti-TB therapy seems to be as effective in HIV-positive as in HIV-negative TB patients. This paper reports on the level and nature of infectious morbidity suffered by HIV-positive patients receiving treatment for TB. The assessment is based upon a sample of inpatients and outpatients at the Infectious Diseases Hospital in Nairobi. Patients were aged 15 years and older, with a TB diagnosis presenting with 1 or more of a series of clinical features. 642 morbid events were seen in 398 patients: 235 HIV-positive patients had 438 event and 163 HIV-negative patients had 204 events. 18% of the HIV-positive patients versus 6% of the HIV-negative patients were bacteremic. Salmonella typhimurium and Streptococcus pneumoniae were most commonly isolated from sera, while fecal specimens were obtained more commonly from HIV-positive patients and often contained bacterial pathogens. The authors conclude that many causes of morbidity in patients with TB and HIV are not due to TB or anti-TB therapy and will not be identified without microbiological investigation. These results suggest that even with effective anti-TB chemotherapy HIV-positive patients will remain or become unwell.