Richard J. Brindle

Life-threatening bacteraemia in HIV-1 seropositive adults admitted to hospital in Nairobi, Kenya

During 6 months, 506 consecutive adult emergency admissions to hospital in Nairobi were enrolled in a study of bacteraemia and HIV infection. 19% were HIV-1 antibody positive. Significantly more HIV-seropositive than seronegative patients had bacteraemia (26% vs 6%). The predominant organisms isolated from the seropositive patients were Salmonella typhimurium and Streptococcus pneumoniae. Mortality was higher in the seropositive than in the seronegative bacteraemic patients. The findings suggest that non-opportunistic bacteria are important causes of morbidity and mortality in HIV-infected individuals in Africa.

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.

The effect of human immunodeficiency virus type-1 on the infectiousness of tuberculosis

SETTING Developing country tertiary referral hospital plus catchment community. OBJECTIVE To determine the infectiousness of culture-confirmed pulmonary tuberculosis in patients infected with Human Immunodeficiency Virus type-1 (HIV-1). DESIGN Comparison of the incidence of tuberculosis and the prevalence of tuberculin skin test positivity among the household contacts of both HIV-1 positive and negative cases with pulmonary tuberculosis. RESULTS Of 255 contacts of HIV-1 negative index cases, 2 were HIV-1 positive and of 102 contacts of HIV-1 positive index cases, 14 were HIV-1 positive (odds ratio (OR) = 20.0 95% Confidence Interval (CI) 4.4-193). 21 cases of tuberculosis were diagnosed among contacts, of whom 3 were HIV-1 positive. The overall unadjusted OR for tuberculosis among contacts of HIV-1 positive index cases was 1.6 (95% CI 0.6-4.3) compared to contacts of HIV-1 negative index cases. Amongst HIV-1 negative contacts alone the OR was 1.5 (95% CI 0.4-4.4). In this group the best predictors of tuberculosis among contacts were female sex of the index case (OR = 3.4 95% CI 1.1-12), sharing the same bed as the index case (OR = 2.6 95% CI 0.9-7.4), and contacts age less than 5 years (OR = 3.3 95% CI 1.1-9.5). HIV-1 positive contacts were more likely to develop tuberculosis than HIV-1 negative contacts (OR = 4.1 95% CI 0.7-17). Tuberculin skin test positivity rates were the same among the HIV-1 negative contacts of HIV-1 positive and negative index cases (OR = 1.1 CI 0.7-1.6). CONCLUSIONS HIV-1 associated pulmonary tuberculosis is not more infectious than tuberculosis alone. The presence of HIV-1 in a community does not mandate a change in the management of contacts of patients with pulmonary tuberculosis.

Extrapulmonary and disseminated tuberculosis in HIV-1-seropositive patients presenting to the acute medical services in Nairobi.

We studied 506 consecutive adult acute medical admissions to hospital in Nairobi; 95 (18.8%) were seropositive for HIV-1, and 43 new cases of active tuberculosis (TB) were identified. TB was clearly associated with HIV infection, occurring in 17.9% of seropositive patients compared with 6.3% of seronegatives [odds ratio (OR) 3.2; 95% confidence limits (CL) 1.6-6.5]. Extrapulmonary disease was more common in seropositive than seronegative TB patients (nine out of 17 versus five out of 26; OR 4.7; 95% CL 1.01-23.6); this accounted for most of the excess cases of TB seen in seropositive patients. Mycobacteraemia was demonstrated in two of eight seropositive TB patients but in none of 11 seronegative TB patients. No atypical mycobacteria were isolated. The World Health Organization (WHO) clinical case definition for African AIDS did not discriminate well between seropositive and seronegative TB cases. Five out of seven seropositive women with active tuberculosis had delivered children in the preceding 6 months and were lactating, compared with only one out of eight seronegative tuberculous women. An association between recent childbirth, HIV immunosuppression and the development of TB is suggested.

Disseminated mycobacterium avium Infection Among Hiv-infected Patients in Kenya

Previous studies from Africa have been unable to identify disseminated Mycobacterium avium complex (MAC) infection in patients with advanced human immunodeficiency virus (HIV) infection. We performed mycobacterial blood cultures and CD4 counts on 48 symptomatic adults with advanced HIV infection admitted to the hospital in Nairobi, Kenya over 4 weeks in 1992. Fourteen patients had mycobacteremia; these patients had significantly lower CD4 counts than the patients with negative cultures (14/mm3 vs. 85/mm3; p < 0.01). Three patients (6%) were bacteremic with M. avium (mean CD4 count, 10/mm3) and 11 (23%) were bacteremic with Mycobacterium tuberculosis complex (MTB) (mean CD4 count, 15/mm3). Thus, M. avium bacteremia was detected significantly less frequently in the study population than MTB bacteremia (p = 0.04). The minimum rate for HIV-associated disseminated M. avium infection in patients admitted to the hospital in Nairobi was estimated to be approximately 1%. Patients with mycobacteremia died or were discharged home sick before the diagnosis was made. Disseminated M. avium does occur in adults with advanced HIV infection in sub-Saharan Africa, but is less common than disseminated MTB.

Cohort study of HIV-positive and HIV-negative tuberculosis, Nairobi, Kenya: comparison of bacteriological results

We have set up a cohort of human immunodeficiency virus (HIV) positive and negative patients with tuberculosis in order to address the problems associated with HIV-related tuberculosis. We present here the results of sputum smear microscopy, culture, mycobacterial identification tests and drug susceptibility assays from specimens taken at presentation. In this selected population of largely pulmonary tuberculosis cases, HIV infection is not associated with significant differences in sputum smear positivity rate, culture positivity rate or initial drug resistance. No atypical mycobacteria were found. Direct sputum smear examination remains specific for the diagnosis of tuberculosis in Kenya in spite of the presence of HIV. HIV infection was not associated with an increase in the proportion of pulmonary cases still culture-positive at 6 months. However a significant increase in the proportion of cases still culture-positive at 6 months was seen in those with initially resistant strains and also in those treated with standard regimen (streptomycin, thiacetazone and isoniazid for 1 month followed by thiacetazone and isoniazid for 11 months, 1STH/11TH) rather than a short-course, rifampicin-containing regimen (rifampicin, pyrazinamide and isoniazid for 2 months, together with streptomycin for the first month and followed by 6 months of thiacetazone and isoniazid, SHRZ/6TH).

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.

Comparative humoral responses to HIV-1 p24gag and gp120env in subjects from East Africa and the UK.

We compared 1616 sera from HIV-1-infected subjects and matched HIV-negative local controls in Uganda, Kenya and the UK. Sera were screened for specific antibody to HIV-1 p24 Gag and gp120 Env proteins and for p24 antigenaemia. In contrast to the UK, the majority of African HIV-1-infected subjects maintained detectable anti-p24 antibodies. However, lower reactivity of anti-p24 was observed in African AIDS patients, compared with those with asymptomatic HIV-1 infection. This reduction in anti-p24 reactivity with more advanced clinical stage was less marked in African HIV-1 infection than in the UK. Correspondingly, p24 antigenaemia was more common in patients with AIDS from the UK than in African patients (65 versus 4%). Reductions in anti-gp120 reactivity were observed in African AIDS patients, compared with the asymptomatic group. However, median reactivity of anti-gp120 in UK patients remained unchanged in both asymptomatic and AIDS subjects. The differences in humoral response to p24 and gp120 between Africa and the UK are semi-quantitative rather than qualitative and could be explained by initial higher antibody response to HIV-1 in African subjects.