Impact of expanded antiretroviral use on incidence and prevalence of tuberculosis in children with HIV in Kenya.

SETTING: Antiretroviral therapy (ART) reduces pulmonary tuberculosis (PTB) in human immunodeficiency virus (HIV) infected children. Recent ART recommendations have increased the number of children on ART. OBJECTIVE: To determine the prevalence and incidence of TB in HIV-infected children after the implementation of expanded ART guidelines. DESIGN: A prospective cohort study including HIV-infected children aged 6 weeks to 14 years was conducted in Kenya. The primary outcome measure was clinically diagnosed TB. Study participants were screened for prevalent TB at enrollment using Kenya's national guidelines and followed at monthly intervals to detect incident TB. Predictors of TB were assessed using logistic regression and Cox proportional hazards regression. RESULTS: Of 689 participants (median age 6.4 years), 509 (73.9%) were on ART at baseline. There were 51 cases of prevalent TB (7.4%) and 10 incident cases, with over 720.3 child-years of observation (incidence 1.4 per 100 child-years). Months on ART (adjusted hazard ratio [aHR] 0.91, P = 0.003; aOR 0.91, P< 0.001) and months in care before ART (aHR 0.87, P= 0.001; aOR 0.92, P < 0.001) were protective against incident and prevalent TB. CONCLUSIONS: ART was protective against TB in this cohort of HIV-infected children with high levels of ART use. Optimal TB prevention strategies should emphasize early ART in children.

Placebo found equivalent to amoxicillin for treatment of acute bronchitis in Nairobi, Kenya: a triple blind, randomised, equivalence trial.

BACKGROUND: Antibiotic treatment is not recommended for acute bronchitis in immunocompetent patients in industrialised countries. Whether these recommendations are relevant to the developing world and to immunocompromised patients is unknown. DESIGN, SETTING AND PARTICIPANTS: Randomised, triple blind, placebo controlled equivalence trial of amoxicillin compared with placebo in 660 adults presenting to two outpatient clinics in Nairobi, Kenya, with acute bronchitis but without evidence of chronic lung disease. MAIN OUTCOME MEASURE: The primary study end point was clinical cure, as defined by a >or=75% reduction in a validated Acute Bronchitis Severity Score by 14 days; analysis was by intention to treat with equivalence defined as

Validation of a new clinical scoring system for acute bronchitis.

INTRODUCTION: Although several clinical prediction rules exist for lower respiratory tract infection (LRTI), few are for acute bronchitis (acute bronchitis) and most have not been validated in high human immunodeficiency virus (HIV) prevalence settings. METHODS: An Acute Bronchitis Severity Score (ABSS) was developed and validated during a randomized trial of antibiotic treatment for acute bronchitis. Ambulatory adults with productive cough of < or =2 weeks at out-patient respiratory disease clinics in Nairobi, Kenya, were recruited and assessed for clinical response to therapy. The ABSS quantitative ratings of LRTI-associated symptoms, physical signs and sputum Gram stain purulence were assessed using standard psychometric tests. RESULTS: The ABSS was evaluated among 649 cases of acute bronchitis; 129 (20%) were HIV-seropositive. The ABSS had small floor and ceiling effects (1.8/0.2) and demonstrated high internal consistency (alpha-coefficient of 0.66) and internal validity, with a mean inter item total correlation of > or =0.25. Effect sizes from baseline to subsequent follow-up visits were large (>0.5). Wheezing and chest pain were associated with higher ABSS values, whereas irrelevant clinical variables were not. CONCLUSION: The ABSS demonstrated good responsiveness, high internal consistency, good correlation with common respiratory signs and symptoms and high discriminatory validity among patients with acute bronchitis in a high HIV-seroprevalence setting.

Clinical presentation among HIV-infected and non-infected adults with community acquired pneumonia in Nairobi.

SETTING: Risk factors for mortality in hospitalized patients with community-acquired pneumonia (CAP) are well known. There are limited data on prognostic indicators among out-patients. OBJECTIVE: To compare the clinical presentation, outcome and prognostic factors for clinical improvement in human immunodeficiency virus (HIV) infected and non-HIV-infected out-patients with CAP. METHODOLOGY: Adults in Nairobi with CAP were treated with erythromycin as first-line therapy. Clinical symptoms were evaluated using a validated CAP-related symptom score (CSS). Clinical improvement was defined as reduction of baseline CSS by > or = 50%. RESULTS: Of 531 adults enrolled with CAP, 422 (79.5%) completed follow-up. Participants had a mean age (+/- SD) of 33.7 +/- 11.4 years, 274 (51.6%) were male and 193 (37%) were HIV-seropositive with a higher baseline CSS (27 vs. 25, P < 0.006). Overall, 196 of 422 (46%) had clinical improvement by 28 days. Factors independently associated with a longer time to clinical improvement included not being married (adjusted hazard ratio [aHR] 0.66, 95% CI 0.48-0.92) and higher baseline CSS (aHR 1.05, 95% CI 1.03-1.06). CONCLUSIONS: HIV-infected and non-infected patients with CAP responded similarly to out-patient treatment, but HIV-infected patients were more likely to present with severe symptoms. Baseline CSS and marital status were predictive of time to clinical improvement.

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.

Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya.

HIV infection has now been consistently identified as the major cause of death in young Africans in both urban and rural areas. In Africa, several studies have defined the clinical presentation of HIV disease but there have only been a limited number of autopsy studies. Because of the scarcity of autopsy data and the possibility of differing type and frequency of opportunistic infections between different geographic locations we set out to study consecutive new adult medical admissions to a tertiary referral hospital in Nairobi and perform autopsies on a sample of HIV-1-positive and HIV-1-negative patients who died in the hospital ward. Basic demographic data were collected on all patients admitted to two acute medical wards over an 11-month period. Final outcome and final clinical diagnoses were recorded at discharge or death. An autopsy examination was requested if the patient died in the ward. Autopsy examination was performed in 75 HIV-1-positive (40 men, 35 women) and 47 HIV-1-negative (28 men, 19 women) adults who died in the hospital. This represented 48.4% of all HIV-1-positive deaths and 33.3% of all HIV-1-negative deaths. Tuberculosis (TB) and bacterial and interstitial bronchopneumonia accounted for 96% of the major pathology in patients found to be HIV-1-positive at autopsy. TB was present in half the HIV-1-positive autopsy patients and was disseminated in over 80% of cases. Meningeal involvement was present in 26% of those with disseminated TB. By contrast, TB was much less common in the HIV-1-negative patients at autopsy in whom bacterial bronchopneumonia and malignancies were the most common pathologies. The type pathology found in the HIV-1-positive autopsy patients was not different than that found in other areas in Africa so far studied.

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.

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.

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.