Adjunctive salvage therapy with inhaled aminoglycosides for patients with persistent smear-positive pulmonary tuberculosis.

A proportion of patients with drug-resistant and drug-susceptible tuberculosis (TB) have sputum that is smear and culture positive for Mycobacterium tuberculosis for a prolonged period of time, despite conventional therapy. Among such patients with refractory TB, an unblinded, observational study was undertaken that used conventional TB therapy and adjunctive aerosol aminoglycosides. Patients with persistent smear- and culture-positive sputum for M. tuberculosis (despite > or =2 months of optimal systemic therapy) were selected for adjunctive treatment via inhalation with aminoglycosides, and microbiological responses were monitored. Thirteen of 19 patients converted to smear negativity during the study: 6 of 7 with drug-susceptible TB and 7 of 12 with drug-resistant TB. Among patients with drug-susceptible TB, the median time to sputum conversion was 23 days, a shorter time than for a population of historical control patients. Recurrent infection was not observed. Adjunctive aerosol aminoglycosides may expedite sterilization of sputum among certain patients with refractory TB and diminish the risk of transmission.

A comparison of outbreak- and nonoutbreak-related multidrug-resistant tuberculosis among human immunodeficiency virus-infected patients in a South African hospital.

Nosocomial multidrug-resistant tuberculosis (MDR-TB) in human immunodeficiency virus (HIV)-infected people is recognized in Europe and America. We report the first such outbreak in South Africa. Six hospitalized women, identified by DNA fingerprinting, were infected with an outbreak strain of MDR-TB while receiving treatment for drug-susceptible tuberculosis. The putative source case was identified as an HIV-positive woman who underwent prolonged hospitalization for chronic cavitary tuberculosis. Compared with other HIV-positive patients in the hospital, outbreak patients were more immunocompromised, had fewer cavitary lung changes, and were less likely to have been treated before. They had high fevers, infiltrative patterns on chest radiographs, and a mean survival of 43 days. When individual isolation is not possible, separating highly immunocompromised patients with first-time tuberculosis from previously treated patients with cavitary lesions and from those with established drug resistance may reduce nosocomial transmission.

Primary HIV infection diagnosed in South Africa masquerading as another tropical disease.

Eleven patients referred to a hospital in South Africa with suspected tropical diseases such as malaria, typhoid fever and South African tick bite fever were found to be suffering from primary human immunodeficiency virus (HIV) infection. Hospital records were reviewed retrospectively in those acutely ill, febrile patients where a clinical suspicion of HIV seroconversion existed and no other diagnosis could be found. A history of recent travel, particularly to malarious areas, was given by most of these patients. The clinical presentation was dominated by high fevers and headaches. The most helpful pointers to primary HIV infection included a characteristic palatal enanthem, leucopenia and thrombocytopenia. Ironically, the history of recent travel appeared to have confounded the diagnosis despite the fact that travel has often been associated with the acquisition of HIV in Africa. Recognition of primary HIV infection masquerading as a tropical disease may result in more frequent diagnosis of this serious condition.

Factors related to in-hospital deaths in patients with tuberculosis.

BACKGROUND: Deaths from tuberculosis (TB) continue to occur despite the availability of effective antimicrobial agents. Multidrug resistance, human immunodeficiency virus (HIV) infection, and delayed therapy have been implicated. OBJECTIVE: To examine clinical factors associated with in-hospital death in patients with active TB. METHODS: A retrospective case-control study was performed on patients admitted to a government hospital in Johannesburg, South Africa, used as a referral center for patients with TB. Eighty patients admitted with TB who died during hospitalization were matched with 80 similar patients with TB who survived hospitalization. Clinical, demographic, and radiological characteristics of each group were compared. RESULTS: In-hospital fatalities were associated with female sex (P=.01), lower admission hemoglobin level (P<.01), and weight (P<.01), and a trend to more extensive infiltrative patterns on chest radiographs. Multidrug resistance, extrapulmonary disease, and HIV infection were unexpectedly not related to in-hospital mortality. High mortality in the first weeks of admission suggested that late presentation was a major factor for in-hospital death. The HIV-infected participants in the study showed less drug resistance than HIV-negative patients (P=.07), equivalent extents of infiltrative patterns on chest radiographs, but much less cavitation and fibrosis (P<.01). CONCLUSIONS: Clinical predictors of early mortality from TB included anemia, low body weight, and extensive infiltrates, while multidrug resistance and HIV infection were not significant factors. Previous exposure to TB and delayed presentation may have influenced our findings. Since patients present late in their illness, aggressive case finding would be important in controlling TB in this population.

Use of ciprofloxacin for successful eradication of bacteremia due to Campylobacter cinaedi in a human immunodeficiency virus-infected person.

A 36-year-old homosexual man who was infected with human immunodeficiency virus presented with a 2-month history of fever and intermittent diarrhea. Stool cultures were negative for bacterial pathogens, ova, parasites, and acid-fast organisms. An initial blood culture became positive after 5 days for a curved, gram-negative rod that was identified later as Campylobacter cinaedi. The patient received a series of antibiotic regimens, including a 2-week course of erythromycin followed by a 2-week course of tetracycline, but follow-up blood cultures continued to yield C. cinaedi. The patient was then treated with a 2-week course of oral ciprofloxacin; he remained asymptomatic 11 weeks later, at which time a blood culture was negative for C. cinaedi. To the best of our knowledge, this is the first documented case of symptomatic bacteremia due to C. cinaedi that was successfully treated with ciprofloxacin.

A streptococcal erythrogenic toxin preparation augments natural killer activity of peripheral blood mononuclear cells.

Natural killer (NK) activity in peripheral blood mononuclear cells is augmented by products released by two different strains of streptococci. This property is due at least in part to an erythrogenic toxin (ET). A preparation of physiologically active ET from strain NY5 group A beta-hemolytic streptococci and streptococcal products (SP) derived from the culture supernatants of ATCC strain 19165 group A streptococci were both potent inducers of NK activity. An anti-serum to ET reacted with two polypeptides in SP, one of which comigrated with ET when analyzed by SDS-PAGE. Using an affinity column with an antiserum to ET known to neutralize its mitogenic properties, the NK-enhancing activity of ET and SP was partly absorbed and was recovered upon elution. These findings suggest that immunologically related ETs in different streptococcal strains play a role in the activation of NK cells. This novel property of streptococci may feature in the pathogenesis of streptococcal infections and their protean manifestations.

Cysticercosis in an urban black South African community: prevalence and risk factors.

Cysticercosis still represents a significant health problem in developing communities, despite supposed improvements in sanitation and personal hygiene. An ELISA for Cysticercosis antibodies was performed on serum from 230 random adult admissions to Baragwanath Hospital. Seventeen patients were seropositive giving a prevalence of 7.39% for this group of urban black South Africans. Twenty-one patients with documented cerebral cysticercosis were selected in order to evaluate risk factors for cysticercosis. Of the risk factors considered only a history of tapeworm infestation appeared to be significant. Even urbanisation has not resulted in n reduction in the prevalence of Cysticercosis and it appears that the disease continues to be endemic in this developing community.

Peripheral blood mononuclear cells from AIDS patients release but do not respond to antigen-stimulated NK-activating lymphokines.

We have previously shown that streptococcal product (SP) extracted from the culture supernatants of Streptococcus pyogenes ATCC 19615 augments NK activity, partly by inducing the release of soluble factors from mononuclear cells. In this study we use SP as an NK stimulant to investigate the mechanism of NK depression in AIDS. We demonstrate that the NK activity of AIDS patients is lower than normal controls and can be significantly enhanced with SP, although not to control levels. The decreased cytotoxicity in AIDS is not due to a depletion of NK cells, nor to the depletion of lymphokines from CD4 cells that are directly involved in NK cell activation. PBMCs from patients with AIDS respond to SP, producing normal levels of NK-enhancing substances in their supernatants. However, upon examining the ability of SP-induced supernatants from control cells to augment the NK activity of cells from AIDS patients, we find significantly less activity in AIDS cells than in control cells, suggesting an intrinsic effector dysfunction of NK cells in AIDS.

HIV-1 infection abolishes CD4 biosynthesis but not CD4 mRNA.

In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.

Mirror image arrangement of the abdominal organs with a left-sided morphologically normal heart.

A twenty year old man is described who has a left-sided liver, a single right-sided spleen, an anomalous inferior vena cava with azygos continuation, and a morphologically normal left-sided heart. These findings emphasise the pitfalls in predicting cardiac abnormalities from other aberrations of anatomical situs.