Samir M. Bhatt

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

Summary: 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‐1positive 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.

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.

Visceral leishmaniasis unresponsive to antimonial drugs II. Response to high dosage sodium stibogluconate or prolonged treatment with pentamidine

Ten Kenyan patients with visceral leishmaniasis unresponsive to sodium stibogluconate, at a dose of 16 to 20 mg Sb/kg body-weight/day given for 30 to 98 days, were treated with 20 mg Sb/kg bw given every eight hours. This regimen was modified or abandoned in six patients because of suspected toxicity, although toxicity was difficult to assess because of intercurrent illness. Toxic effects included lethargy, anorexia, vomiting, electrocardiographic changes, fall in haemoglobin and rise in liver enzymes. One patient died, probably from a cardiac arrhythmia. Two patients were cured, four responded partially and four showed no response. Pentamidine, at a dose of 4 mg/kg body-weight given one to 3 times per week for 5 to 39 weeks, was given as initial treatment in one patient and after failure of sodium stibogluconate in seven. Toxic effects included nephritis, hepatitis, transient diabetes and subcutaneous abscesses. Two patients were cured, two responded partially, three showed no response and one, after apparent cure, relapsed and was unresponsive to additional pentamidine treatment. Low-frequency, long-duration pentamidine was often useful in maintaining any improvement made during treatment with the less well tolerated high-dose, high frequency sodium stibogluconate. We observed the step-wise development of resistance to both sodium stibogluconate and pentamidine. The problems of managing patients with visceral leishmaniasis which is unresponsive to conventional doses of pentavalent antimonials are discussed and some tentative suggestions put forward.

Visceral leishmaniasis unresponsive to antimonial drugs I. Clinical and immunological studies

Ten Kenyan patients with visceral leishmaniasis, unresponsive to sodium stibogluconate at a dose of 16 to 20 mg Sb/kg/day given for 30 to 98 days, have been studied clinically and immunologically and compared with 57 antimony-responsive patients. Pulmonary tuberculosis and previous treatment with antimonial drugs were the only factors which were more common in unresponsive patients. The degree of immunosuppression and rate of recovery of immunoreactivity did not differ between antimony-responsive and -unresponsive patients. Only one patient had never been treated before (primary unresponsiveness). In the other nine patients secondary unresponsiveness occurred after one or more treatment courses, suggesting that the parasite developed resistance to antimony. Antimony-unresponsiveness in visceral leishmaniasis is a serious problem numerically, clinically and economically. A plea is made that the initial treatment of visceral leishmaniasis should be adequate in dose and duration.

Prevention of Hearing Loss in Experimental Pneumococcal Meningitis by Administration of Dexamethasone and Ketorolac

Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss. Recent literature has suggested that a vigorous host immune response to Streptococcus [corrected] pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis. This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin. Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo. Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level [SPL] vs. placebo: 33. 4-dB SPL, P=.0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs. placebo: 53.4-dB SPL, P=.0003). These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection.

The changing impact of HIV/AIDS on Kenyatta National Hospital, Nairobi from 1988/89 through 1992 to 1997.

ObjectiveConsequences of the growing HIV/AIDS epidemic for health services in sub-Saharan Africa remain poorly defined. Longitudinal data from the same centre are scarce. We aimed to describe the impact of a rapidly rising HIV/AIDS disease burden on an urban hospital over the last decade. Design and settingCross-sectional observational study in 1997, compared to similar data from 1988/89 and 1992. The study was carried out in the Kenyatta National Hospital, Nairobi, Kenya. MethodConsecutive adult medical patients were enrolled on admission and then followed up until death or discharge. The main outcome measures were clinical stage, HIV status, bacteraemia, length of stay, bed occupancy, final diagnosis and outcome of hospital admission. ResultsIn 1997, 518 patients, 493 with HIV serology, were enrolled: HIV prevalence was 40.0%, bed occupancy 190%, the mean length of stay 9.5 days (SD 12) and overall mortality 18.5%. The mean number of HIV-positive admissions per day steadily rose from 4.3 [95% confidence interval (CI), 0.6] patients in 1988/89, through 9.6 (95% CI, 1.4) in 1992, to 13.1 (95% CI, 2.8) or 13.9 adjusted for those enrolled without HIV serology in 1997. In contrast the mean number admitted with clinical AIDS, 1.7 in 1988/89 and 3.3 in 1992, fell to 2.6 cases per day in 1997. With HIV-negative admissions increasing by 37% and bed occupancy nearly doubling in 1997, HIV prevalence appeared to be stabilizing (19 then 39 and 40% respectively). Over time fewer HIV-infected patients were bacteraemic (26, 24 and 14%;P < 0.01); had clinical AIDS (39, 34 and 24% respectively;P < 0.01); or died (36, 35 and 22.6%;P < 0.02). HIV-negative mortality, 14% in 1988/89, rose to 23% in 1992 but fell to 15% in 1997. The mean length of hospital stay (9.5–10 days) did not differ according to HIV status nor did it change across the decade. ConclusionThe HIV/AIDS disease burden in Kenyatta National Hospital medical wards has risen inexorably over the last decade. Most recently, the number of HIV-uninfected patients has also risen, leading to bed occupancy figures of 190%. Despite overcrowding and irrespective of HIV status, in-patient mortality has fallen. Time trends suggest fewer clinical AIDS patients are presenting for hospital care, implying a rising community burden of chronic HIV/AIDS disease. Although widely predicted, it is not inevitable that medical services in urban African hospitals dealing with large volumes of HIV/AIDS disease, will collapse or become overwhelmed with chronic, end-stage disease and death.

The impact of dexamethasone on hearing loss in experimental pneumococcal meningitis.

Bacterial meningitis, particularly that resulting from Streptococcus pneumoniae, is a common cause of acquired profound sensorineural deafness in children. The pathogenesis of meningogenic hearing loss has been investigated in an experimental rabbit model. In this study significant deafness was documented within the first 15 hours of infection. Initiation of antibiotic therapy at this time diminished the severity of hearing loss in most animals. The addition of dexamethasone to antibiotic therapy prevented the development of profound deafness. These results suggest this model will be useful in developing antiinflammatory strategies to improve the outcome of bacterial meningitis.

Costs of hospital care for HIV-positive and HIV-negative patients at Kenyatta National Hospital, Nairobi, Kenya.

ObjectiveTo record the costs of hospital care for HIV-positive and -negative patients in Nairobi, and identify costs paid by patients per admission. DesignCost data were collected on inpatients enrolled in a linked clinical study using standardized costing methods. SettingKenyatta National Hospital, Nairobis main district hospital. PatientsConsecutive adult medical admissions to one ward over 14 weeks who consented to enrolment; tertiary referrals were excluded. Main outcome measureAverage length of stay and cost per patient admission. ResultsThe hospital costs of 398 patients (163 HIV positive; 33 with clinical AIDS) were analysed. The mean length of stay was 9.3 days and the mean cost per patient admission was US

Angiolymphoid hyperplasia with eosinophilia (histiocytoid hemangioma): Evaluation of treatment options

163. There was no significant difference in costs or mean lengths of stay between HIV-positive and -negative groups, nor were the costs and lengths of stay for clinical AIDS patients significantly different to those for HIV-positive patients without AIDS. The patient charges paid to the hospital per admission, recorded for 344 patients, were on average US

Malignant triton tumor of the head and neck.

61; and did not differ by HIV status. ConclusionThe similar cost patterns for inpatient care irrespective of HIV status or clinical AIDS probably reflects the limited provision of care beyond basic clinical services. Length of stay rather than differing treatment regimes thus appears to be the main cost driver. Private costs of medical care were high and were likely to pressurize households. When resources are limited, the introduction of new, more costly therapies needs careful planning. The study provides cost information for planning care services in resource-poor settings.