Robert Colebunders

Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings

The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important early complication of antiretroviral therapy (ART) in resource-limited settings, especially in patients with tuberculosis. However, there are no consensus case definitions for IRIS or tuberculosis-associated IRIS. Moreover, previously proposed case definitions are not readily applicable in settings where laboratory resources are limited. As a result, existing studies on tuberculosis-associated IRIS have used a variety of non-standardised general case definitions. To rectify this problem, around 100 researchers, including microbiologists, immunologists, clinicians, epidemiologists, clinical trialists, and public-health specialists from 16 countries met in Kampala, Uganda, in November, 2006. At this meeting, consensus case definitions for paradoxical tuberculosis-associated IRIS, ART-associated tuberculosis, and unmasking tuberculosis-associated IRIS were derived, which can be used in high-income and resource-limited settings. It is envisaged that these definitions could be used by clinicians and researchers in a variety of settings to promote standardisation and comparability of data.

Ebola Hemorrhagic Fever in Kikwit, Democratic Republic of the Congo: Clinical Observations in 103 Patients

During the 1995 outbreak of Ebola hemorrhagic fever in the Democratic Republic of the Congo, a series of 103 cases (one-third of the total number of cases) had clinical symptoms and signs accurately recorded by medical workers, mainly in the setting of the urban hospital in Kikwit. Clinical diagnosis was confirmed retrospectively in cases for which serum samples were available (n = 63, 61% of the cases). The disease began unspecifically with fever, asthenia, diarrhea, headaches, myalgia, arthralgia, vomiting, and abdominal pain. Early inconsistent signs and symptoms included conjunctival injection, sore throat, and rash. Overall, bleeding signs were observed in <45% of the cases. Typically, terminally ill patients presented with obtundation, anuria, shock, tachypnea, and normothermia. Late manifestations, most frequently arthralgia and ocular diseases, occurred in convalescent patients. This series is the most extensive number of cases of Ebola hemorrhagic fever observed during an outbreak.

Treatment of Ebola Hemorrhagic Fever with Blood Transfusions from Convalescent Patients

Between 6 and 22 June 1995, 8 patients in Kikwit, Democratic Republic of the Congo, who met the case definition used in Kikwit for Ebola (EBO) hemorrhagic fever, were transfused with blood donated by 5 convalescent patients. The donated blood contained IgG EBO antibodies but no EBO antigen. EBO antigens were detected in all the transfusion recipients just before transfusion. The 8 transfused patients had clinical symptoms similar to those of other EBO patients seen during the epidemic. All were seriously ill with severe asthenia, 4 presented with hemorrhagic manifestations, and 2 became comatose as their disease progressed. Only 1 transfused patient (12.5%) died; this number is significantly lower than the overall case fatality rate (80%) for the EBO epidemic in Kikwit and than the rates for other EBO epidemics. The reason for this low fatality rate remains to be explained. The transfused patients did receive better care than those in the initial phase of the epidemic. Plans should be made to prepare for a more thorough evaluation of passive immune therapy during a new EBO outbreak.

Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo

We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic fever in an area of confirmed Marburg virus transmission in the Democratic Republic of the Congo. Questionnaires were administered and serum samples tested for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103 participants in a targeted antibody survey of healthcare workers were antibody negative. Primary transmission of Marburg virus to humans likely occurred via exposure to a still unidentified reservoir in the local mines. Secondary transmission appears to be less common with Marburg virus than with Ebola virus, the other known filovirus.

Persistent diarrhoea in Zairian AIDS patients: an endoscopic and histological study.

To determine the aetiology of persistent diarrhoea in African patients with acquired immunodeficiency syndrome (AIDS), 42 patients with human immunodeficiency virus (HIV) and persistent diarrhoea were enrolled in a microbiological, endoscopic, and histological study. Cryptosporidium was the intestinal parasite most often identified (30%); Isospora belli was found in 12% of the patients. Histological examination of the duodenal mucosa showed a non-specific inflammatory reaction in a significantly higher number of HIV-seropositive patients (82%) than HIV-seronegative controls without diarrhoea (52%) (p = 0.02). Lymphocytes were more likely to be found in inflammatory reactions in HIV-seropositive patients than in controls (p less than 0.0001). Pathogens were observed in histological sections of the duodenum of HIV-seropositive patients only (p = 0.002) and included cryptosporidia (four patients) Isospora belli (one), Strongyloides stercoralis (one), and Cryptococcus neoformans (one). On histological examination the rectal mucosa of HIV-seropositive patients and controls was similar, except eosinophils were more likely to be present in inflammatory reaction in HIV-seropositive patients (p = 0.05) and enteric pathogens were observed only in HIV-seropositive patients (cytomegalovirus inclusion bodies (one) and Schistosoma mansoni (two). The aetiology of persistent diarrhoea in most African AIDS patients remains unclear.

Late Ophthalmologic Manifestations in Survivors of the 1995 Ebola Virus Epidemic in Kikwit, Democratic Republic of the Congo

Three (15%) of 20 survivors of the 1995 Ebola outbreak in the Democratic Republic of the Congo enrolled in a follow-up study and 1 other survivor developed ocular manifestations after being asymptomatic for 1 month. Patients complained of ocular pain, photophobia, hyperlacrimation, and loss of visual acuity. Ocular examination revealed uveitis in all 4 patients. All patients improved with a topical treatment of 1% atropine and steroids.

Organization of Patient Care during the Ebola Hemorrhagic Fever Epidemic in Kikwit, Democratic Republic of the Congo, 1995

In contrast with procedures in previous Ebola outbreaks, patient care during the 1995 outbreak in Kikwit, Democratic Republic of the Congo, was centralized for a large number of patients. On 4 May, before the diagnosis of Ebola hemorrhagic fever (EHF) was confirmed by the Centers for Disease Control and Prevention, an isolation ward was created at Kikwit General Hospital. On 11 May, an international scientific and technical committee established as a priority the improvement of hygienic conditions in the hospital and the protection of health care workers and family members; to this end, protective equipment was distributed and barrier-nursing techniques were implemented. For patients living far from Kikwit, home care was organized. Initially, hospitalized patients were given only oral treatments; however, toward the end of the epidemic, infusions and better nutritional support were given, and 8 patients received blood from convalescent EHF patients. Only 1 of the transfusion patients died (12.5%). It is expected that with improved medical care, the case fatality rate of EHF could be reduced.

Heterosexual transmission of HIV-1 among employees and their spouses at two large businesses in Zaire.

To better understand the reasons why up to 80% of all HIV-1 infections in Zaire, but less than 5% in North America and Europe, are acquired through heterosexual transmission, and to assess the impact of HIV-1 infection on a large urban African workforce, we enrolled 7068 male employees, 416 female employees and 4548 female spouses of employees at two large Kinshasa businesses (a textile factory and a commercial bank) in a prospective study of HIV-1 infection. The HIV-1 seroprevalence rate was higher in male employees (5.8%) and their spouses (5.7%) at the bank than among male employees (2.8%) and their spouses (3.3%) at the textile factory. At both businesses HIV-1 seroprevalence was higher among employees in managerial positions (5.0%) than among workers in lower-level positions (3.0%; P less than 0.0001). In a multivariate analysis of male employees, receipt of a transfusion, a history of genital ulcer disease, working at the bank, urethritis, or being divorced or separated were independently associated with HIV-1 infection. During 1987 and 1988, AIDS was the most common cause of death among recently employed workers, accounting for 20 and 24% of all deaths at the textile factory and the commercial bank, respectively. The HIV-1 seroprevalence rate was higher among female workers (7.7%) than among the spouses of male workers (3.9%; P = 0.001). In multivariate analysis of the wives of workers, having an HIV-1-seropositive spouse, receipt of a blood transfusion, or a history of genital ulcer disease were independently associated with HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Marburg Hemorrhagic Fever in Durba and Watsa, Democratic Republic of the Congo: Clinical Documentation, Features of Illness, and Treatment

The objective of the present study was to describe day of onset and duration of symptoms of Marburg hemorrhagic fever (MHF), to summarize the treatments applied, and to assess the quality of clinical documentation. Surveillance and clinical records of 77 patients with MHF cases were reviewed. Initial symptoms included fever, headache, general pain, nausea, vomiting, and anorexia (median day of onset, day 1-2), followed by hemorrhagic manifestations (day 5-8+), and terminal symptoms included confusion, agitation, coma, anuria, and shock. Treatment in isolation wards was acceptable, but the quality of clinical documentation was unsatisfactory. Improved clinical documentation is necessary for a basic evaluation of supportive treatment.

Corticosteroid Therapy, Vitamin D Status, and Inflammatory Cytokine Profile in the HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

Vitamin D deficiency is common in human immunodeficiency virus–tuberculosis coinfected patients in Cape Town. Those who develop tuberculosis-immune reconstitution inflammatory syndrome have a further reduction in circulating 25-hydroxyvitamin D levels 2 weeks into combined antiretroviral therapy with a concomitant increase in inflammatory cytokines and chemokines.