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Biomedical subjects

M Hoelscher

Publications and source records attributed to M Hoelscher.

At least 19 recordsLinked to original sources
PubMed2005

Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis.

A direct antigen-capture ELISA based on the detection of mycobacterial lipoarabinomannan (LAM) in unprocessed urine was evaluated for its usefulness in clinical practice. In Tanzania, 231 patients with suspected pulmonary tuberculosis (TB) and 103 healthy volunteers were screened with standard TB tests and with the new LAM-ELISA. Of 132 patients with confirmed pulmonary mycobacterial disease (positive sputum culture), 106 were positive using the LAM-ELISA (sensitivity 80.3%). In comparison, the sensitivity of acid-fast bacilli (AFB) sputum microscopy was 62.1% (82 of 132 confirmed cases). Of the 231 patients, 17 were both culture- and AFB-negative, but had typical radiographic signs of pulmonary mycobacterial infection and did not respond to antibiotic treatment. Of these 17 patients, 13 (76.5%) had positive LAM-ELISA test results. To define the specificity of the assay, urine samples from 103 healthy volunteers were also screened using LAM-ELISA. All but one had an optical density below the cut-off (specificity 99%). Of interest was a significant correlation between level of microscopic density of mycobacteria in sputum and LAM antigen concentration in urine (chi2=8.44). The LAM-ELISA is a field-adapted tool that can improve screening standards in countries with a high incidence of TB.

AIDS-Related Opportunistic Infections↗
PubMed2005

In-depth, longitudinal analysis of viral quasispecies from an individual triply infected with late-stage human immunodeficiency virus type 1, using a multiple PCR primer approach.

Co-infections with more than one human immunodeficiency virus type 1 (HIV-1) subtype appear to be the source of new recombinant strains and may be commonplace in high-risk cohorts exposed to multiple subtypes. Many potential dual infections have been identified during the HIV Superinfection Study in Mbeya, Tanzania, where 600 female bar workers who are highly exposed to subtypes A, C, and D have been evaluated every 3 months for over 3 years by use of the MHAacd HIV-1 genotyping assay. Here we describe an in-depth, longitudinal analysis of the viral quasispecies in a woman who was triply infected with HIV-1 and who developed AIDS and passed away 15 months after enrollment. The MHA results obtained at 0, 3, 6, 9, and 12 months revealed dual-probe reactivities and shifts in subtype over time, indicating a potential dual infection and prompting further investigation. The multiple infection was confirmed by PCR amplification of three genome regions by a multiple primer approach, followed by molecular cloning and sequencing. A highly complex viral quasispecies was found, including several recombinant forms, with vpu/gp120 being the most diverse region. A significant fluctuation in molecular forms over time was observed, showing that the serial sample format is highly desirable, if not essential, for the identification of multiple infections. In a separate experiment, we confirmed that the detection of co-infections is more efficient with the use of multiple amplification primers to overcome the primer bias that results from the enormous diversity in the HIV-1 genome.

Acquired Immunodeficiency Syndrome↗
PubMed2005

In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months postinfection.

Human immunodeficiency virus type 1 (HIV-1) superinfection refers to the acquisition of another strain by an already infected individual. Here we report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multi-region genotyping assay. The subject was identified in the window period and was first infected with a complex ACD recombinant strain, became superinfected 6 to 9 months later with an AC recombinant, and was monitored for >2.5 years. The plasma viral load exceeded 400,000 copies/ml during the first 9 months of infection but resolved to the set point of 67,000 copies/ml by 3 months after superinfection; the CD4 cell count was 377 cells/mul at 30 months. Viral diversity was evaluated with techniques designed to fully sample the quasi-species, permitting direct observation of the evolution, temporal fluctuation, and intercompartment dynamics of the initial and superinfecting strains and recombinants derived from them. Within 3 months of superinfection, seven different molecular forms were detected in gag and six were detected in env. The proportions of forms fluctuated widely over time in plasma and peripheral blood mononuclear cells, illustrating how challenging the detection of dually infected individuals can be. Strain-specific nested PCR confirmed that the superinfecting strain was not present until the 9 month follow-up. This study further defines the parameters and dynamics of superinfection and will foster appropriate studies and approaches to gain a more complete understanding of risk factors for superinfection and its impact on clinical progression, epidemiology, and vaccine design.

Evolution, Molecular↗
PubMed2004

Methodological lessons from a cohort study of high risk women in Tanzania.

OBJECTIVES: To describe the development, characteristics, and follow up of a high risk cohort of women in Tanzania. Differences in social background and sexual behaviour of women working in traditional and modern alcohol selling workplaces are shown. METHODS: Data from questionnaires four months before the enrollment of the cohort, at enrollment, and at 32 months were compared. Key informant interviews, social mapping exercises, and focus group discussions were held before the start of the cohort. RESULTS: In the absence of organised prostitution, two different groups of women with high risk exposure were identified during the baseline survey: female workers in modern alcohol selling places such as bars, guesthouses, and restaurants (barmaids) and in traditional places (local brew sellers). Overall, the population had a mean age of 27.7 years with barmaids tending to be younger (24.3 years) than local brew sellers (34.2 years). The main duration of stay in the current workplace was 2.1 years (barmaids 0.9 years; local brew sellers 4.1 years). Barmaids were more likely to have paying casual sex partners than local brew sellers and used condoms more regularly. Local brew sellers tend to be more stable with only 10% lost to follow up after 32 months compared with 24.4% of the bar workers. CONCLUSIONS: Preliminary work revealed major differences in characteristics and behaviour between women working in modern and traditional alcohol selling outlets. Thorough preparation of the study, close monitoring of the cohort, and provision of selected benefits resulted in high retention rates over a 32 month project in a highly mobile population.

Adult↗
PubMed2003

Baseline survey of sexually transmitted infections in a cohort of female bar workers in Mbeya Region, Tanzania.

OBJECTIVES: To determine baseline prevalence of sexually transmitted infections (STI) and other reproductive tract infections (RTI) and their association with HIV as well as sociodemographic and behavioural characteristics in a newly recruited cohort of female bar workers in Mbeya Region, Tanzania. METHODS: 600 female bar workers were recruited from 17 different communities during September to November 2000 and underwent gynaecological examination, laboratory testing for HIV/STI, and interviews using structured questionnaires. RESULTS: HIV-1 seroprevalence was 68%. Prevalences of STI/RTI were high titre syphilis (TPPA/RPR >/=1/8), 9%; herpes simplex virus 2 antibodies, 87%; chlamydia, 12%; gonorrhoea, 22%; trichomoniasis, 24%; and bacterial vaginosis, 40%. HIV infection was associated with TPPA and HSV-2 seropositivity, bacterial vaginosis and clinically diagnosed genital ulcers, blisters, and warts. Reported high risk sexual behaviour during the past year (having multiple casual partners) was associated with prevalent STI. CONCLUSION: Female bar workers in Mbeya are at high risk of STI and HIV infection. Targeted STI/HIV prevention interventions for these women and their sexual partners need to be reinforced. Methods should be sought to improve healthcare seeking and to provide easily accessible and affordable STI care services.

Adult↗
PubMed2002

Sensitivity and specificity of ELISA and immunoblot for diagnosing neurocysticercosis.

In patients with neurocysticercosis (NCC), clinical manifestations and the results of neuroimaging procedures vary widely and often do not facilitate a definite diagnosis. In order to determine the value of immunodiagnosis for NCC, 222 serum and cerebrospinal fluid samples from patients with NCC and healthy subjects were examined. The samples represented patients from various endemic regions, those with other neurological disorders from an endemic area (Mexico), persons with various helminth infections other than NCC, and a group of healthy volunteers. All specimens were tested by enzyme-linked immunosorbent assay and immunoblot for the presence of Taenia solium-specific antibodies. The sensitivities of the enzyme-linked immunosorbent assay and the immunoblot test in NCC patients were almost identical (80% and 81.7%, respectively). For both tests, the sensitivity was higher when cerebrospinal fluid (86%) was tested compared with serum (75%). The overall specificity of enzyme-linked immunosorbent assay was only 75.3% because of frequent false-positive results in patients with other helminth infections, especially in those with echinococcosis. The specificity (99.4%) of the immunoblot test was clearly superior. It is concluded that enzyme-linked immunosorbent assay as a screening method and immunoblot as a confirmatory test contribute considerably to the diagnosis of NCC.

Animals↗
PubMed2002

Anti-saccharomyces cerevisiae antibodies in patients with inflammatory bowel disease and their first-degree relatives: potential clinical value.

Anti-Saccharomyces cerevisiae antibodies (ASCA) have been described as specific markers in Crohn's disease and their healthy first-degree relatives. 171 patients with Crohn's disease, their 105 first-degree relatives, 145 patients with ulcerative colitis and 101 first-degree relatives of patients with ulcerative colitis, 50 patients with infectious enterocolitis and 100 healthy controls were tested for ASCA employing the ELISA technique. When compared with the healthy controls (p < 0.0001) and patients with infectious enterocolitis (p < 0.0001) the prevalence of ASCA was significantly increased in patients with Crohn's disease and their first-degree relatives (p < 0.01). Further significant differences concerning the frequency of ASCA within the different groups of our study population were not observed. In particular, ASCA were not found in increased prevalence in infectious enterocolitis. These observations are compatible with a role of ASCA as a marker of genetic predisposition to Crohn's disease.

Adult↗
PubMed2001

High proportion of unrelated HIV-1 intersubtype recombinants in the Mbeya region of southwest Tanzania.

BACKGROUND: In Mbeya, a rural region of southwest Tanzania, HIV-1 subtypes A, C and D have been co-circulating since the early 1990s. OBJECTIVE: To define to what extent the co-existence of subtypes has led to recombinant HIV-1 strains and whether there is evidence for epidemic spread of any circulating recombinant form. METHODS: Nine HIV-1-seropositive young adults from Mbeya Town with no evident high-risk behaviour contributed peripheral blood mononuclear cells for this study. Nine virtually full-length-genome-sequences were amplified from this DNA and phylogenetically analysed. RESULTS: Out of the nine samples, two were subtype A (22%), two were subtype C (22%) and five were recombinants (56%): four A/C recombinants and one C/D recombinant. None of the recombinants were related to each other; all of them had different mosaic structures. Most of the genome in the recombinants was subtype C. CONCLUSION: A high proportion of unrelated intersubtype recombinants, none of them apparently spreading in the population, may be present in southwest Tanzania.

Adolescent↗
PubMed2000

Endothelial cell autoantibodies are a marker of disease susceptibility in inflammatory bowel disease but apparently not linked to persistent measles virus infection.

Intestinal vasculitis caused by persistent measles virus infection of intestinal endothelial cells was described in Crohn's disease. Furthermore, endothelial cell autoantibodies have been demonstrated in inflammatory bowel disease (IBD). Autoantibodies against intestinal endothelial cells were visualized by indirect immunofluorescence in patients with IBD, in their healthy first-degree relatives, in patients with infectious enterocolitis, and in healthy, unrelated controls. In intestinal tissue specimens of 22 antibody-positive IBD patients a search for the measles virus genome was performed. Endothelial cell autoantibodies were significantly more frequent in patients with IBD, in both groups of first-degree relatives, and in patients with infectious enterocolitis than in the healthy controls (P = 0.0002 or less). The measles virus genome was found in none of the intestinal biopsies. Endothelial cell autoantibodies are not a genetic but rather an epigenetic (infectious) marker of disease susceptibility. The expression of these autoantibodies is unlikely to be triggered by a persistent measles virus infection.

Adolescent↗
PubMed1998

HIV type 1 V3 serotyping of Tanzanian samples: probable reasons for mismatching with genetic subtyping.

HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Estimating the number of HIV transmissions through reused syringes and needles in the Mbeya Region, Tanzania.

OBJECTIVE: HIV infection attributable to medical injections is suspected to be low, although case-control studies have not provided definite results. This study aims to determine the number of HIV infections caused by the reuse of syringes and needles in the Mbeya Region, Tanzania. METHODS: The direct identification or detection of HIV in syringes and needles under field conditions was not appropriate, therefore a surrogate marker consisting of two components for possible HIV transmission was used: insufficient sterilization, and blood remaining from a previous patient. The assumption was that HIV infection can only occur if both markers are positive. Samples were collected in nine health-care facilities. All syringes and needles prepared for use in these facilities were collected without prior notification. The samples were rinsed and the resulting fluid was cultured for bacteria. Traces of blood were detected by urine stick test for haemoglobin volumes > 0.0015 microliters. RESULTS: Bacterial contamination was found in 32.8% of the total 1219 syringes and needles; 67% was caused by improper handling of the equipment after sterilization. Blood was detected in 12.5% of the samples. In the following three sampling strata, both contamination criteria were positive either on the syringe or the needle: wards/outpatient departments (OPD), 1.39%; laboratories, 7.45%; expanded programme on immunization (EPI), < 0.1%. We calculated that from 1.1 million patients injected in wards/OPD in any 1 year, fewer than 13 become infected, in laboratories fewer than 12 (160,000 blood-taking procedures), and less than one child in the EPI (850,000 vaccinations). CONCLUSION: With an established AIDS intervention programme supporting the health system, less than 0.4% of the total annual incidence of 4500-8500 is attributable to medical injections in the Mbeya Region.

Case-Control Studies↗
PubMed1977

Fungus infections after liver transplantation.

The problem of fungus infections after liver transplantation was studied. In 100 consecutive recipients of orthotopic liver homografts there were 10 and 8 examples, respectively, of localized and disseminated infections caused by Candida species. Candidemia was demonstrated in 8 of these 18 patients. One patient who had a localized Candida infection also had disseminated cryptococcosis. An additional 31 patients were infested in that Candida could be cultured from sites where it is not normally found, such as the blood (8 examples), urine (8), ascitic fluid (8), and wounds (22). This exorbitant incidence of monilial infections and infestations was associated with a high frequency of complications involving the homograft as well as the hosts' gastrointestinal tract during the post-transplantation period. The yeasts found in blood, urine, ascitic fluid and elsewhere were thought to have originated from the gut. Ten of the 100 patients had aspergillosis which was localized in 7 instances and disseminated in 3. The lung was the most frequently affected organ. The fungus infections played a contributory role in the downhill course of our patients but in the event of death more fundamental and more frequent causes of failure were technical complications involving the homografts, difficulties in controlling rejection with reasonable immunosuppressive doses and bacterial sepsis. Suggestions have been made for the better control of fungal infections in liver recipients.

Ascitic Fluid↗