African AIDS Patients Research Articles

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.

CD14(+) macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide.

BackgroundIntestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT).MethodsPhenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman’s correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn’s post-test and the Mann–Whitney U tests.ResultsNone of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-α and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS.ConclusionsIntestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.

Companion Drugs for Amphotericin B in Cryptococcal Meningitis: Flucytosine, Fluconazole, or…Nothing?

Companion Drugs for Amphotericin B in Cryptococcal Meningitis: Flucytosine, Fluconazole, or…Nothing?

Pulmonary cryptococcosis misdiagnosed as smear-negative pulmonary tuberculosis with fatal consequences

HIV-associated pulmonary cryptococcosis is under diagnosed, and may progress to fatal meningoencephalitis. We present a case of HIV-associated pulmonary Cryptococcus neoformans infection, initially mis-diagnosed as smear-negative pulmonary TB, which progressed to fatal cryptococcal meningitis. Autopsy series suggest that pulmonary cryptococcosis is common in African AIDS patients, and, due to limited diagnostic capacity, often mis-diagnosed as smear negative TB. Serum cryptococcal antigen testing may facilitate diagnosis in such cases.

Antifungal activities of selected Venda medicinal plants against Candida albicans, Candida krusei and Cryptococcus neoformans isolated from South African AIDS patients.

Infection with HIV leads to immunosuppression and up to 90% of HIV infected individuals contract fungal infections of which 10 - 20% die as a direct consequence of these infections. In the present study, 76 extracts from 30 plants used by Venda traditional healers for the treatment of fungal related ailments, were tested for their antifungal activities against clinical isolates of Candida albicans, Candida krusei and Cryptococcus neoformans using the agar diffusion and the microdilution methods. The minimum fungicidal concentrations as well as the time kill curves of the thee most active plants were also determined. Extracts from 25 plants (83.3%) were active against C. albicans, C. krusei or C. neoformans. Thirty two extracts were active against C. neoformans, while 15 were active against C. albicans and 12 were active against C. krusei. Warburgia salutaris, Cassine transvaalensis, Piper capense, Maerua edulis, Pseudolachnostylis maprouneifolia, Berchemia discolor and Lippia javanica were not only inhibitory to fungal growth but also had fungicidal effects against one or all the 3 fungi tested (MIC/MFC between 0.11 and 7.5 mg/ml). Hexane extracts were also active indicating that many of the antifungal components of these plants are non-polar compounds. Time-to- kill experiments indicated an intense time-dependent fungicidal effect against C. albicans, achieving over a 5 h-period a 6 log10-unit decrease in CFU/ml at a concentration of 0.4 mg/ml for W. salutaris. The present study justifies the traditional use of these plants for the treatment of opportunistic infections in the region.

Improved detection of JC virus in AIDS patients with progressive multifocal leukoencephalopathy by T‐antigen specific fluorescence resonance energy transfer hybridization probe real‐time PCR: Evidence of diverse JC virus genotypes associated with progressive multifocal leukoencephalopathy in Southern Africa

JC virus (JCV) causes progressive multifocal leukoencephalopathy under conditions of immunosuppression, especially associated with HIV. Despite the high prevalence of HIV-1 infection, few cases of progressive multifocal leukoencephalopathy have been reported and only a small number of JCV strains have been characterized in AIDS patients in Southern Africa. Diagnosis of progressive multifocal leukoencephalopathy through PCR detection of JCV DNA in CSF may result in false negative results if variable regions of the genome are targeted. Characterization of circulating JCV genotypes in Southern Africa may assist with designing appropriate diagnostic assays and characterizing the molecular epidemiology of JCV in African AIDS patients. In this study, a new real-time PCR using fluorescence resonance energy transfer hybridization probes targeting the conserved large T-antigen was developed and compared to a conventional nested PCR targeting the variable VP1 region. Validation against known JCV positive specimens confirmed its specificity while amplification of a serial dilution of JCV control DNA suggests that the new real-time PCR can detect lower concentrations of JCV than the VP1 nested PCR. Investigation of CSF specimens from 44 suspected progressive multifocal leukoencephalopathy patients suggest that the new assay is more sensitive being able to detect JCV in 12 specimens versus 5 specimens with the VP1 nested PCR. Sequence analysis confirmed that the T-antigen region is completely conserved while phylogenetic analysis of the five VP1 products identified two genotype 3, one genotype 1 and two genotype 4 strains, the latter two identified for the first time in South African AIDS patients.

Genotypic Characterization and Comparison of Full-Length Envelope Glycoproteins from South African HIV Type 1 Subtype C Primary Isolates That Utilize CCR5 and/or CXCR4

CCR5 has preferentially been used by all circulating HIV-1 subtype C viruses for cell entry. Recently, we reported the highest proportion of CXCR4-utilizing primary isolates among a cohort of 20 South African AIDS patients. This study describes and compares the Env genotypic characteristics from these 20 HIV-1 subtype C (and unique CD recombinant) primary isolates. Fourteen primary isolates utilized CCR5, four (including the CD recombinant) used CXCR4, and two were dual tropic. Extensive analysis and comparison of important structural motifs such as the N-linked glycosylation sites, signal sequences, CD4-binding sites, variable loops, cleavage sites, known neutralizing antibody and small molecule inhibitor binding sites confirmed that other than the expected differences in the V3 loop, no sequence motifs distinguished between R5 and X4 tropism. Further correlation of the env genotype to functionally relevant motifs is necessary to elucidate the relationship between biologically and immunologically relevant sites and aid vaccine and novel drug design.

Emergence of X4 usage among HIV-1 subtype C: evidence for an evolving epidemic in South Africa

This study investigated the genotype and phenotype of HIV-1 isolates of 20 South African AIDS patients. We found the highest percentage of CXCR4 usage among primary isolates, in which 30% efficiently utilized CXCR4 and exhibited the syncytium-inducing phenotype. Phylogenetic analysis of env confirmed that 19 of the 20 were subtype C, and syncytium-inducing viruses had genetic changes in the V3 loop, characteristic of CXCR4 usage. Results imply that the frequency of CXCR4-utilizing subtype C is increasing with time.

Effect of GB virus C co-infection on response to generic HAART in African patients with HIV-1 clade C infection

In 38 African AIDS patients initiating generic HAART, GB virus C (GBV-C) RNA-positive patients retained GBV-C viraemia during 52 weeks of HAART, had a faster decline in HIV viral load (P = 0.03), fewer opportunistic infections (14.3 versus 50%, P = 0.18), and suffered no serious adverse events (none versus 61%, P = 0.008) compared with patients without GBV-C. GBV-C co-infection may be associated with a beneficial effect on African AIDS patients treated with generic HAART.

Electron Microscopy Reveals Fungal Cells Within Tumor Tissue from Two African Patients with AIDS-associated Kaposi Sarcoma

Electron microscopic investigation of biopsy materials from Kaposi sarcoma (KS) skin lesions of 2 African AIDS patients occasionally revealed fungal cells within the tumor tissue. The spherical cells were surrounded by a triple-layered cell wall and were not encapsulated. The ultrastructural characteristics of the cells resemble those of Candida albicans organisms. Neither patient showed clinical signs of a generalized fungal infection. The presence of Candida albicans in the KS tissue specimens seems to represent an early and asymptomatic stage of cutaneous candidiasis in the 2 severely immunocompromised AIDS patients.

HIV-1 Subtype C, CCR5-using Viruses are Detected in CD4T Cells and Macrophages in South African AIDS Patients. Analysis by Fluorescent In Situ Hybridization and V3 Loop Sequencing

Background In South Africa, HIV-1 subtype C is the prevalent subtype and has been found to use CCR5 throughout the viral infection in most cases1. In contrast, HIV-1 subtype B often switches its coreceptor usage to CXCR4 due to mutations primarily within the V3 loop of the gp120 protein2. In order to assess whether subtype C is still able to infect T cells in late stages of the infection, FISH was used to localize HIV sequences within different blood cell types of AIDS patients.

Phylogenetic evidence of widespread distribution of genotype 3 JC virus in Africa and identification of a type 7 isolate in an African AIDS patient.

JC virus (JCV) is the cause of progressive multifocal leukoencephalophathy (PML) in immunocompromised patients. The paucity of reports from Africa has led to the hypothesis that PML is rare because of an absence of virus genotypes associated with the condition. Genotypes 3 and 6 have been identified in East and West Africa but the distribution of types across the rest of Africa is unknown. Full-length sequences of five JCV cerebrospinal fluid samples from PML patients in South Africa are reported here. Three isolates from African AIDS patients grouped with type 3A or 3B, and one with type 7, while one from a Caucasian leukaemia patient grouped with type 2D. Widespread distribution of type 3 on the continent may reflect migration patterns in antiquity, but this is the first report of type 7 in an African individual. Type 2D has only been isolated previously in South Asia, although transmission of this genotype to Europeans who later settled in South Africa is not unlikely.

Ocular disease in patients with TB and HIV presenting with fever in Malawi

To investigate ocular disease in Malawian patients with tuberculosis (TB) and HIV in presenting with fever, and to determine if indirect ophthalmoscopy is useful in the diagnosis of mycobacteraemia. A prospective study of all adult patients admitted with fever to Queen Elizabeth Central Hospital, Blantyre. All recruited patients had an ophthalmic examination, HIV tests, chest x-ray, sputum examinations, bacterial and mycobacterial blood cultures and malaria slide. 307 patients were recruited; 109 (36%) had TB, including 53 (17%) with mycobacteraemia; 255 (83%) had HIV and 191 (62%) had AIDS. Of the patients with TB 102 (94%) had HIV. Choroidal granulomas were found in four patients, all of whom had AIDS; three had disseminated TB with mycobacteraemia, and one had persistent fever but no other evidence of TB. Among the patients with AIDS, 32 (17%) had retinal microangiopathy manifest by cotton wool spots; one (0.5%) had signs of active cytomegalovirus (CMV) retinitis. The presence of microangiopathy was not related to TB. In Malawian patients with TB presenting acutely with fever, choroidal granulomas were found in 2.8%, and were concurrent with mycobacteraemia and AIDS. Ophthalmoscopy was not a useful aid in the diagnosis of mycobacteraemia. CMV retinitis is rarely seen in African AIDS patients. This may be due to mortality early in the disease course, or differences in race, HIV sub-type or co-morbidity.

Global Development

New WTO's Policy to Protect Public Health Interests for Developing Countries. Drugmakers from India Helping African AIDS Patients Comply to Therapy. GE Acquires Amersham as Part of Strategic Expansion.

Albendazole chemotherapy for AIDS‐related diarrhoea in Zambia—clinical, parasitological and mucosal responses

Albendazole reduces diarrhoea in African AIDS patients, but it is unclear if the clinical response to treatment reflects pathogen eradication and/or mucosal recovery. Adults with HIV-related persistent diarrhoea were treated with albendazole 800 mg twice daily for 14 days. Clearance of parasites was evaluated at 3 and 6 weeks by stool microscopy. At baseline and at 6 weeks duodenal biopsies were taken for electron microscopy (EM) and morphometry. Ten (7%) of 153 patients had cryptosporidiosis, 54 (37%) had isosporiasis and 23 (16%) had microsporidiosis. By 3 weeks, these protozoa were cleared in 27 (46%) of 59 patients initially positive. By 6 weeks, 34 (39%) of 87 patients experienced complete clinical response, 18 (21%) partial response and 35 (40%) no response. Crypt depth increased by 15% over 6 weeks (P < 0.001), but villous height increased only in patients with complete response (median + 50 microm, interquartile range (IQR) 2-90, compared to patients with partial (+ 4 microm, IQR -15,41) or no response (-13 microm, IQR -2,12; P=0.008)). Fifteen patients died: body mass index < 17.5 kg/m(2) and crypt depth < 180 microm independently predicted death. Albendazole therapy reduced the burden of protozoal infection and promoted mucosal recovery in patients with a complete clinical response.

Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions

SETTINGInpatient medical wards, Department of Medicine, University Teaching Hospital, Lusaka, Zambia.OBJECTIVETo define the natural history, clinical presentation, and management outcome of microbiologically confirmed cryptococcal meningitis in adult AIDS patients treated...

Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions

Abstract SETTING Inpatient medical wards, Department of Medicine, University Teaching Hospital, Lusaka, Zambia. OBJECTIVE To define the natural history, clinical presentation, and management outcome of microbiologically confirmed cryptococcal meningitis in adult AIDS patients treated under local conditions where antifungal and antiretroviral therapies are not routinely available. Design A descriptive, longitudinal, observational study. METHODS All adult patients admitted to the medical wards of the University Teaching Hospital, Lusaka, Zambia with cerebrospinal fluid culture proved, primary cryptococcal meningitis, during a 12 month period were enrolled into the study. The following details were acquired: clinical features, HIV status, laboratory data, treatment accorded, and survival. Results A total of 230 patients with primary cryptococcal meningitis were studied (median age 32 years; range 15–65 years; 112 males, 118 females). Cryptococcal meningitis was the first AIDS defining illness in 210 (91%) patients. One hundred and thirty of the 230 (56%) patients had received treatment with fluconazole monotherapy and 100 (43%) patients received palliative care only without any antifungal therapy. A 100% case fatality rate was observed in both groups at follow up: by seven weeks in the untreated group and at six months in the fluconazole treated group. The cumulative median survival from time of diagnosis was 19 days (range 1–164 days) for the fluconazole treated group and 10 days (range 0–42 days) for the untreated group. Conclusion Cryptococcal meningitis, under current treatment accorded at the University Teaching Hospital, Lusaka, has a 100% mortality in young Zambian adults with AIDS. The current treatment accorded to Zambian adults with cryptococcal meningitis is inappropriate. An urgent need exists to improve strategies for the clinical management of AIDS patients in poor African countries. The wider ethical and operational issues of making available antifungals to African AIDS patients are discussed.

Clinicopathological features of cutaneous histoplasmosis in human immunodeficiency virus-infected patients in Zimbabwe

Reports of disseminated Histoplasma infection in African AIDS patients are scanty. In Zimbabwe, 12 patients presented in 1994–2000 with facial nodular/papular cutaneous lesions, which became umbilicated and finally ulcerated. Histology revealed non-granulomatous inflammation and macrophages stuffed with Histoplasma. Recognition of these clinical features may lead to more rapid diagnosis of disseminated histoplasmosis in Africa.

African AIDS tragedy: Patent rights versus human rights

Pharmaceutical researchers have recently developed drugs that have helped extend the life spans of many AIDS patients. These drugs include the human immunodeficiency virus (HIV) protease inhibitors. Unfortunately, many people in African countries and other developing nations cannot afford to use such medicines. According to both the Joint United Nations Program on HIV/AIDS (UNAIDS) and the World Health Organization (WHO), 70% of people newly infected with HIV in 1998 live in southern Africa. About 83% of all AIDS deaths have occurred there since the epidemic began, although only 10% of the world's population lives there. About 11.5 million southern African AIDS patients had died by the end of last year—almost 2 million in 1998 alone. With the advent of protease- inhibitor drugs and the concept of combination therapy, many AIDS patients in the U.S. and Europe are now able to live reasonably productive lives. But in many developing countries, one year's HIV treatment, if it ...

The epidemiology of CMV retinitis in Africa

AIM: To analyze the prevalence of cytomegalovirus (CMV) retinitis in African AIDS patients. METHOD: A Medline survey was carried out to identify reports on the ocular manifestations of HIV infection in African patients. Relevant information on CMV retinitis was identified and analyzed. RESULTS: The reported prevalence of CMV retinits in African AIDS patients varies from 0 to 8.5%. CONCLUSION: The low prevalence of CMV retinitis in Africa compared to Europe and the United States suggests that most African patients either die from other diseases before they enter the stage of severe immune depression associated with CMV disease or their survival at this stage is very short. This also explains why bilateral and hence blinding CMV retinitis is rare among African AIDS patients.