J. Kimari

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.

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 × 106/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.

Trends in Bloodstream Infections among Human Immunodeficiency Virus-Infected Adults Admitted to a Hospital in Nairobi, Kenya, during the Last Decade

Bloodstream infections are a frequent complication in human immunodeficiency virus (HIV)-infected adults in Africa and usually associated with a poor prognosis. We evaluated bloodstream infections across a decade in 3 prospective cross-sectional surveys of consecutive medical admissions to the Kenyatta National Hospital, Nairobi, Kenya. Participants received standard clinical care throughout. In 1988-1989, 29.5% (28 of 95) of HIV-positive patients had bloodstream infections, compared with 31.9% (46 of 144) in 1992 and 21.3% (43 of 197) in 1997. Bacteremia and mycobacteremia were significantly associated with HIV infection. Infections with Mycobacterium tuberculosis, non-typhi species of Salmonella (NTS), and Streptococcus pneumoniae predominated. Fungemia exclusively due to Cryptococcus neoformans was uncommon. Clinical features at presentation remained similar. Significant improvements in the survival rate were recorded among patients with NTS bacteremia (20%-83%; P<.01) and mycobacteremia (0%-73%; P<.01). Standard clinical management can improve outcomes in resource-poor settings.

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.

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.

Analysis of Salmonella enterica serotype Typhimurium by phage typing, antimicrobial susceptibility and pulsed-field gel electrophoresis

Three typing methods commonly used for bacteria--phage typing, antimicrobial susceptibility and pulsed-field gel electrophoresis (PFGE)- were used to characterise 64 Salmonella enterica serotype Typhimurium isolates from individual adult patients from Nairobi, Kenya. The isolates encompassed 11 definitive phage types (DTs), which fell into eight PFGE clusters; 31.3% of isolates were either untypable or reacted nonspecifically with the phages used for typing and 26.6% were of DT 56. Plasmids of c. 100 kb were responsible for self-transferable multiresistance among the isolates. Analysis by PFGE and phage type demonstrated that multiresistant Typhimurium strains causing diarrhoea and invasive disease were multiclonal.

Serotypes and antibiotic susceptibilities of Streptococcus pneumoniae in Nairobi, Kenya

Two hundred and sixteen clinically significant isolates of Streptococcus pneumoniae from 138 adult patients attending clinics in Nairobi, Kenya over a 2 year period were characterized by antibiotic sensitivity testing and serotyping. Overall antibiotic resistance rates were: penicillin, 25%; tetracycline, 34%; erythromycin, 0%; chloramphenicol, 0.4%. Minimum inhibitory concentrations (MICs) of penicillin ranged from < 0.008-0.5 microgram/ml. Determination of penicillin resistance (MIC > or = 0.1 microgram/ml) by oxacillin 1 microgram disc diffusion zone diameter < or = 20 mm was 100% sensitive, 92% specific. Relative resistance to oxacillin (MIC range 0.25-1.0 microgram/ml) accounted for penicillin sensitive isolates determined falsely to be penicillin resistant by oxacillin disc testing. Penicillin resistance was more frequent in sputum isolates at 35% than in blood isolates at 18% (P = 0.013). Serotypes 6, 10, 14, 16, 19 and 23 were associated with penicillin resistance. This study provides information of value for planning management strategies for pneumococcal disease from an area where there are few existing data.

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.

Carriage of potentially pathogenic Escherichia coli in chickens

SUMMARY. DNA-DNA hybridization, cultured cell lines, and transmission electron microscopy were used to study pathogenicity traits of 64 Escherichia coli isolated from apparently healthy chickens from 18 small-scale farms in Thika District, Kenya. A total of 39 (60.9%) isolates hybridized with the eae gene probe for enteropathogenic E. coli (EPEC) whereas another 16 (25%) hybridized with the lt and st gene probes and were categorized as enterotoxigenic E. coli. Electron microscopic examination of the eae probe-positive E. coli cultures with the HT-2919A cell line confirmed that they were able to attach intimately and produced effacement typical of EPEC. In addition, negative stain electron microscopy showed that the EPEC strains produced pili that have previously been associated with increased virulence of E. coli infections in chickens. This study has also demonstrated that apparently healthy chickens may carry enteropathogenic E. coli strains.

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.