Antimicrobial activity of selected plants against fungal species isolated from South African AIDS patients and their antigonococcal activity.

Background Sexually transmitted infections continue to be a major health concern in sub-Saharan Africa where antimicrobial drugs are becoming ineffective due to increasing resistance. Many healthcare seekers in lower socio-economic settings depend on invasive alien plants administered by traditional health practitioners to treat sexually transmitted infections. Methods Roots of selected plants were analysed for phytoconstituents using standard methods. Both the disc diffusion model and microdilution technique were used to determine the inhibition zone and minimum inhibitory concentration (MIC) of plant extracts against six clinical fungal strains and standard strain of Neisseria gonorrhoea. One-way ANOVA was used to find significant differences. Results Different phytoconstituents such as alkaloids, steroids, cardiac glycosides, terpenes, flavonoids, tannins and saponins were qualitatively detected, depending on plant species. Acetone extracted the highest number of phytoconstituents in Senna didymobotrya, while methanol revealed most from Ricinus communis. Senna didymobotrya showed significant inhibition against Candida glabrata, C. krusei, C. parapsilosis and C. tropicalis. Dichloromethane extract of Catharanthus roseus and methanol extract of S. didymobotrya demonstrated excellent MIC values of 0.03 and 0.08 mg/mL, respectively, against C. glabrata. Catharanthus roseus, Opuntia ficus-indica and Ricinus communis demonstrated moderate to good antigonococcal activity, with all exhibiting more than 63% inhibition. Catharanthus roseus had the best antigonococcal activity with a moderate MIC value of 0.63 mg/mL. Conclusion Some of the plant extracts demonstrated potency towards clinically isolated fungal strains and against N. gonorrhoea, which validate the notion that some of the species need further pharmacological studies for isolation and characterisation of active compounds.

Ferments and the AIDS virus: interspecies counter-conduct in the history of AIDS.

In the first three decades after AIDS started infecting people in the USA and Canada, before, during and after the emergence of anti-retroviral therapies, numerous "alternative and holistic treatments" for AIDS were debated, tested, circulated, written about and taught. This paper, taking a narrow focus, examines documents that reveal how some people with AIDS developed a logic of care predicated on intimate interactions with microscopic lifeforms-the AIDS virus and the bacteria involved in fermentation, in particular. Focusing on the writings of Jon Greenberg and Sandor Katz, two former members of ACT UP/NY, I show that the men did not just dissent from management by biomedical authority but found new authority about how to care for themselves as people with AIDS from their interactions with non-human microscopic life. The practices and writings of both men demonstrate that Foucault's theory of counter-conduct exists in the history of AIDS as an interspecies process in which microscopic existents lead humans. From Katz and Greenberg, I argue there is an interspecies dimension to counter-conduct that exists as a frame for understanding people who find in non-human life a guide towards unconventional forms of care, revised forms of human behaviour and philosophies for persisting with illness.

[Effect of xiaomi granules in treating 40 patients of HIV/AIDS oral candidiasis].

OBJECTIVE: To observe the effect of xiaomi granules (XMG) for treatment of HIV/AIDS oral candidiasis. METHODS: Forty patients in the treated group were treated by XMG and 40 patients in the control group were treated with anticandine. The therapeutic course for both groups was two weeks. Changes of clinical symptoms, oral candida microscopic examination and cultured before and after treatment as well as the safety of treatment were observed, and a follow-up study was implemented two weeks after ending medication to compare the relapse rate between groups. RESULTS: Symptoms as oral greasy-sticky, thirsty, asthenia, abdominal distension and anorexia were improved after treatment in both groups (P < 0.05). The improvements of oral greasy-sticky and thirsty in the treated group were better than those in the control group (P < 0.05). The effective rate and relapse rate in the treated group was 90.0% (36/40) and 11.1% (4/36) respectively, while in the control group, 72. 5% (29/40) and 31.0% (9/29) respectively. CONCLUSION: XMG could improve the clinical symptoms with high efficacy and low relapse rate, shows a better effect than that of anticandine in treating HIV/AIDS oral candidiasis.

Caring for the caregivers: models of HIV/AIDS care and treatment provision for health care workers in Southern Africa.

Rollout of antiretroviral therapy (ART) has been successfully initiated in many countries, but concerns have been raised about the ability to meet treatment needs in areas where there is a high prevalence of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) and where there are severe deficits in human-resource capacity. Many health care workers in resource-poor areas are experiencing burnout, struggling with external and internal stigma, failing to access HIV testing and treatment early, and subsequently becoming sick and dying of AIDS. Although the human-resource deficit is a well-recognized problem, little has been written about the programs that have been established to provide treatment for HIV-infected health care workers. In the present article, we describe staff care programs at McCord Hospital in Durban, South Africa; Mseleni Hospital in northern KwaZulu-Natal, South Africa; and the Tshedisa Institute in Gaborone, Botswana. These programs provide convenient, confidential, and holistic care for HIV-infected health care workers and health care workers affected by caring for HIV-infected patients. All 3 programs have noted that, among health care workers, there is increasing acceptance of counseling, testing, and treatment. We propose that there is an urgent need for the development of HIV/AIDS care and treatment programs for health care workers that remove barriers to access, provide confidentiality in testing, are conveniently located, and are integrated with tuberculosis programs and other treatment services.

Anti-Cryptococcus activity of combination of extracts of Cassia alata and Ocimum sanctum.

The paper reports the anti-Cryptococcus activity of combination of ethanolic extracts of leaves of Cassia alata and Ocimum sanctum. The activity of combination of the extracts was heat-stable and worked at acidic pH.

Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology.

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of < 200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration, > or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans.

Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.

Molecular karyotyping of multiple yeast species isolated from nine patients with AIDS during prolonged fluconazole therapy.

Variations in molecular karyotype and fluconazole susceptibility of serial yeast isolates from the oral cavities of nine patients with AIDS receiving fluconazole for single or multiple episodes of oropharyngeal candidiasis were monitored. Multiple yeast species were isolated from the initial oral specimens in six patients. Molecular karyotyping identified at least eight different DNA subtypes of C. albicans, at least eight of T. glabrata and only one DNA subtype each of C. krusei, C. tropicalis and C. parapsilosis. Among isolates of T. glabrata, fluconazole MICs in each patient were consistently within one or two dilutions, regardless of strain variations. Similarly, among five patients monitored during one course of therapy, the MICs of fluconazole of C. albicans isolates of either the same or different DNA subtypes remained within two dilutions. However, increases in MICs of fluconazole of C. albicans were observed in four patients who received two or more courses of fluconazole, three of whom had the same DNA subtype and one of whom changed from one DNA subtype to another.

[Investigation of AZT susceptibility of sequential HIV-1 isolates from patients treated with ddI after long-term therapy with AZT].

AZT susceptibility of sequential 12 HIV-1 isolates was investigated by culture method. These isolate were obtained from three patients who had received AZT for at least 12 months and switched to ddI after they appeared to deteriorate clinically. Cultures of isolate from a patient before therapy with AZT or ddI did not show cytopathic effect (CPE) in the presence of 0.1 microM or 1.0 microM AZT. Culture of 2 isolates from two patients treated with AZT more than 6 months before switched to ddI therapy showed CPE in the presence of AZT and HIV-1 p24 antigen was detected by ELISA in the supernatants. Culture of 6 of 7 isolates from three patients treated with ddI after long-term therapy with AZT also showed CPE in the presence of 1.0 microM AZT and HIV-1 p24 antigen was detected. These results demonstrated that AZT-resistant variant was still a dominant population in the isolate from patients after 11 to 13 months of discontinuing AZT therapy.

pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo.

Specific mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene that cause zidovudine (3'-azido-2',3'-dideoxythymidine; AZT) and didanosine (2',3'-dideoxyinosine; ddI) resistance were studied. The 50% inhibitory concentrations (IC50s) of nucleosides for cloned viruses containing these mutations were compared with the IC50s of the corresponding triphosphate analogs for mutant recombinant-expressed reverse transcriptases (RTs). Changes in ddATP inhibition of RNA-dependent DNA polymerase activity fully accounted for the ddI resistance of the virus caused by a Leu-74-->Val substitution in RT, including an augmentation by the AZT-selected substitutions Thr-215-->Tyr and Lys-219-->Gln in RT. In contrast, the AZT-selected substitutions studied did not cause as great a change in the IC50 of AZT-triphosphate (AZT-TP) for polymerase as they did in the IC50 of AZT for mutant virus. In addition, the mutation at codon 74 suppressed AZT resistance in the virus caused by the mutations at codons 215 and 219 but did not suppress the AZT-TP resistance of enzyme containing these same mutations in RT. The mutation at codon 74 was found in clinical isolates whether or not the patient had received AZT prior to starting ddI therapy. AZT resistance coexisted with ddI resistance following acquisition of Leu-74-->Val in three clinical isolates, indicating that the suppressive effect of Val-74 on the AZT resistance of the virus does not occur in all genetic contexts. When this suppression of AZT resistance was seen in the virus, Val-74 did not appear to cause mutually exclusive changes in AZT-TP and ddATP binding to RT in vitro. The results of the in vitro experiments and characterization of clinical isolates suggest that there are differences in the functional effects of these AZT and ddI resistance mutations.

High-level resistance to zidovudine but not to zalcitabine or didanosine in human immunodeficiency virus from children receiving antiretroviral therapy.

Human immunodeficiency virus type 1 (HIV-1) isolates from children receiving long-term therapy with an alternating regimen of zidovudine and zalcitabine, or with didanosine monotherapy, were evaluated for resistance to zidovudine, zalcitabine, and didanosine, and for mutations known to be associated with zidovudine or didanosine resistance. HIV-1 from four of six patients receiving zidovudine with zalcitabine developed high-level resistance to zidovudine. A mutation in the HIV-1 reverse transcriptase that is highly associated with zidovudine resistance was identified in all four zidovudine-resistant posttherapy isolates. In contrast, none of the HIV-1 isolates from the seven patients receiving didanosine developed high-level resistance to this agent, despite the identification of a didanosine-associated mutation in six of these posttherapy isolates, although small decreases in sensitivity to didanosine were observed. These results indicate that nucleoside analog-associated mutations in HIV-1 occur frequently in children receiving long-term antiretroviral therapy and that alternating combination therapy does not prevent the development of resistance to zidovudine. They also suggest that there may be differences in the degree of resistance conferred by mutations that result from therapy with different nucleoside analogs. These findings underscore the need for studies to define the clinical importance of these mutations, and for treatment strategies to overcome the emergence of viral resistance in vivo.

Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice.

Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities. When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections. KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M. intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence. Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M. intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed. When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M. intracellulare N-241, N-256, and N-260. In this case, the efficacy was the highest in N-260 infection, followed by strain N-241. When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment. However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection. This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study.

Acyclovir resistance/susceptibility in herpes simplex virus type 2 sequential isolates from an AIDS patient.

The biological characterization of a number of sequential herpes simplex virus type 2 (HSV-2) isolates obtained from an AIDS patient undergoing sequential courses of antiviral treatment due to an extended mucocutaneous genital lesion is reported. Resistance to acyclovir (ACV) and related compounds was linked to a thymidine kinase-deficient (TK-) phenotype. After ACV discontinuation and a course of treatment with foscarnet, a new isolate was recovered, characterized by loss of the ACV-resistant trait and production of a functional TK enzyme. Data presented stress the need for monitoring chemosensitivity of HSV isolates in AIDS patients while suggesting that for better control of the infection, these patients should benefit from alternative treatments with drugs aimed at different viral targets.

Susceptibility of bacterial isolates from AIDS patients to six fluoroquinolones.

The susceptibilities to ciprofloxacin, DR-3355 (S-(-)-ofloxacin), enoxacin, lomefloxacin, ofloxacin and PD127,391 of 69 significant bacterial isolates from HIV-positive patients at the City Hospital, Edinburgh have been determined. With the exception of the enterococci, most of the strains tested (including staphylococci, Escherichia coli and Pseudomonas aeruginosa) were susceptible to the fluoroquinolones. Ciprofloxacin was the most active of the clinically available drugs followed by ofloxacin, lomefloxacin and enoxacin. PD127,391 and DR-3355, the new fluoroquinolones tested, were at least as active as ciprofloxacin. Hence bacterial infections in AIDS patients should respond to fluoroquinolone therapy.

Rheumatological lesions in individuals with human immunodeficiency virus infection.

One hundred and twenty-three patients with human immunodeficiency virus infection have been referred to rheumatologists at our hospitals between October 1985 and April 1989 because of musculoskeletal symptoms. Thirty-four homosexual men presented with acute, peripheral, non-erosive arthritis (mean number of four joints affected) with the knees being involved in 23. Other features developing concurrently with arthritis included psoriasis, keratoderma blenorrhagica, plantar fasciitis, urethritis, conjunctivitis and anterior uveitis. Four of five patients investigated were HLA-B27-positive; none of 15 patients tested had raised titres of rheumatoid or antinuclear factors. Various infections were associated with the onset of arthritis and two patients with a recent history of diarrhoea had serological evidence of yersinia infection. No micro-organisms were identified within the joint except for HIV itself. At the time of onset of arthritis four of these individuals had the acquired immunodeficiency syndrome (AIDS); 11 were not known to be HIV-positive before testing which was performed following referral for arthritis. Six patients have since developed AIDS and four have died. In 15 individuals, including those who progressed to AIDS, joint symptoms have been severe, persistent and poorly responsive to non-steroidal anti-inflammatory drugs. In only five patients has the arthritis been known to resolve. Synovitis has also been seen in two women: in one of these HIV infection was thought to have been acquired through intravenous drug abuse. Other rheumatic lesions included myalgia/myositis, non-inflammatory peripheral arthritis, spinal pain, soft tissue lesions, arthralgia or myalgia of unknown cause and infective lesions including septic arthritis and bony infection due to histoplasmosis and atypical mycobacterial infection. It appears likely that HIV infection is a risk factor for the development of seronegative arthritis and other rheumatic lesions.

Comparative in-vitro activity of twenty antimicrobial agents against clinical isolates of Mycobacterium avium complex.

The in-vitro susceptibility of Mycobacterium avium complex isolates, obtained from immunosuppressed patients with and without the Acquired Immunodeficiency Syndrome (AIDS), to various antimicrobial agents was determined. Amikacin, the 4-quinolone compounds--ciprofloxacin, temafloxacin and PD 117558--and the penem SCH 34343 were active against most of the isolates. In-vitro synergism using selected antimicrobial combinations could not be demonstrated. No differences in the susceptibility, depending upon the source of the isolates (AIDS or non-AIDS), were noted.

Methods of autologous blood transfusion.

Fear of AIDS has been a major factor in the re-examination of the methods of autologous blood transfusion. Four techniques are currently available, one of which, the pre-operative donation scheme, has supplied 70 per cent of participants' total blood requirements at operation.

Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

Ten patients with acquired immunodeficiency syndrome with newly diagnosed cytomegalovirus (CMV) retinitis were treated with an induction regimen of intravenous foscarnet, 60 mg/kg of body weight, administered as a 2-h infusion and repeated every 8 h for 14 days. At the end of induction, 9 of 10 patients had stabilized (no new retinal lesions and stable old lesions [7 patients]) or improved (decreased retinal opacification [2 patients]). All eight patients with CMV in urine or blood upon entry into the study had negative urine and blood cultures at the end of induction. After induction therapy, seven patients continued maintenance foscarnet therapy, 60 mg/kg as a single daily infusion, 5 days/week. In six patients, retinal lesions increased in size after 2 to 32 weeks of maintenance therapy. One was invaluable because a retinal detachment developed. Only 9 of 42 blood and urine cultures obtained during maintenance foscarnet therapy yielded CMV, compared with 7 of 14 obtained prior to the initiation of foscarnet induction therapy (P = 0.04). Foscarnet toxicity was mild and infrequent: elevation in serum creatinine by 0.5 to 1.3 mg/dl over the base line (two patients), muscle twitching (three patients), hemoglobin decrease by 1 mg/dl (two patients), nausea (two patients), absolute neutrophil count decrease by 50% (one patient), rise in serum phosphorus to greater than 5.5 mg/dl (four patients), and proteinuria (two patients). Intermittently administered intravenous foscarnet appears to be an effective, relatively nontoxic therapy for CMV retinitis. Additional studies to determine the optimal dosage for maintenance therapy are needed, as are comparative trials with ganciclovir.