Chronic diarrhoea among HIV-infected adult patients in Nairobi, Kenya.

OBJECTIVES: Chronic diarrhoea and wasting are well recognized features of AIDS in Africa. However, because of resource constraints few comprehensive aetiological studies have been conducted in sub-Saharan Africa which have included a broad range of microbiological investigations. We undertook a prospective cross-sectional study of adult patients admitted to a government hospital in Nairobi, Kenya, to determine possible bacterial, mycobacterial, parasitic and viral causes of diarrhoea; to consider which may be treatable; and to relate microbiological findings to clinical outcome. METHODS: Stool specimens from 75 consecutive HIV-seropositive patients with chronic diarrhoea admitted to a Nairobi hospital were subjected to microbiological investigation and results were compared with clinical findings and outcome. Stool samples were cultured for bacteria and mycobacteria and underwent light and electron microscopy; lawns of Escherichia coli were probed for pathogenic types and aliquots were tested for the presence of Clostridium difficile cytotoxin. Blood cultures for mycobacteria and other bacterial pathogens were performed as clinically indicated. RESULTS: Thirty-nine (52%) patients yielded putative pathogens, the most common being Cryptosporidium sp. (17%), Salmonella typhimurium (13%), and Mycobacterium tuberculosis (13%). Of 41 patients investigated for pathogenic Escherichia coli, enteroaggregative E. coli and diffusely adherent E. coli were each found in four patients. Thirty-one (41%) patients died. Detection of cryptosporidium cysts was the single most significant predictor of death (X2 = 5.2, P<0.05). Many patients did not improve (21; 28%) or self-discharged whilst still sick (5; 7%) but five (7%) were diagnosed ante mortem with tuberculosis and treated and a further 13 (17%) showed improvement by time of discharge. CONCLUSIONS: HIV-infected patients with chronic diarrhoea in Nairobi have a poor outcome overall, and even with extensive investigation a putative pathogen was identified in only just over half the patients. The most important step is to exclude tuberculosis; and the most useful investigation appears to be Ziehl-Neelsen staining. Other potentially treatable gram-negative bacterial pathogens, S. typhimurium, Shigella sp. and adherent E. coli were, however, common but require culture facilities which are not widely accessible for definitive identification. Further studies focussing on simple ways to identify sub-groups of patients with treatable infections are warranted.

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.

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.

Identification of urinary pathogens by the RAPIDEC ur system.

A commercial method (RAPIDEC ur; bioMérieux UK Ltd, Basingstoke) and an in-house scheme based on conventional tests were compared for the identification of 179 commonly encountered gram-negative urinary pathogens. The methods identified correctly to genus level 97% and 84% of organisms, respectively. RAPIDEC ur was superior at identifying Escherichia coli, due to the detection of beta-glucuronidase activity, but less cost-effective than the in-house scheme.

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.

Biochemical mis-identification of Brucella melitensis and subsequent laboratory-acquired infections.

Brucella species are mis-identified in the API 20NE system as Moraxella phenylpyruvica (profile number 1200004). Since some Brucella spp. grow readily in routine blood culture medium and may be isolated from patients without clinically obvious brucellosis, the risk of laboratory-acquired brucellosis exists. We describe two such cases.