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Biomedical subjects

C Gilks

Publications and source records attributed to C Gilks.

At least 19 recordsLinked to original sources
PubMed2004

Polyuria in association with Plasmodium falciparum malaria in a region of unstable transmission.

During a recent epidemic of Plasmodium falciparum malaria in Hlabisa district, KwaZulu Natal, polyuria was recognized in a subset of adults presenting to hospital with severe disease. In January to May 2000, following consent, cases of severe malaria provided blood spots for HIV testing, clinical data, and blood and urine samples for investigation of the polyuria. Four hundred and eleven adults with malaria were admitted, of whom 175 had severe malaria and 37 had polyuria (21% of severe cases). In those with polyuria the mean 24-h urine output was 3018 ml or 2.85 ml/kg/h. Ten of 15 (66%) patients investigated had urine and plasma osmolalities consistent with diabetes insipidus. There was no significant association between polyuria and sex, age, HIV status or features of severe malaria. Whether the polyuria in these non-immune adults is a localized problem unrelated to malaria, or a hitherto unrecognized complication of severe malaria is not clear. Physicians are alerted to this observation, and the need for more clinical and pathophysiological studies.

Adult↗
PubMed2002

Diarrhea, CD4 counts and enteric infections in a community-based cohort of HIV-infected adults in Uganda.

OBJECTIVES: To examine relationships between diarrhoea, CD4 cell counts and stool pathogens in a community-based cohort of HIV-infected adults in Uganda. PATIENTS AND METHODS: Stool specimens, obtained between October 1995 and December 1997, were linked to patients' symptoms and laboratory results. The relationship between CD4 counts and symptoms was tested using the Wilcoxon rank-sum test and those between organisms and diarrhoea using first a univariate Mantel-Haenszel analysis and then a logistic regression model adjusted for CD4 count and multiple organisms. RESULTS: 1,213 HIV-infected individuals (70% women, median CD4 cell count at enrollment 215 cells/microl) were followed for 1,224 person years of observation (pyo). 484 stool samples were examined, 357 from patients with diarrhoea. The rate of diarrhoea was 661 episodes per 1,000 pyo. CD4 counts were significantly lower in individuals with diarrhoea than those without (P < 0.001, Wilcoxon rank-sum test). Forty-nine percent of diarrhoeal stools and 39% of stools from asymptomatic patients contained enteric pathogens. The most frequent isolates were helminths (29.5% of all stools), followed by bacteria (19.2%) and then protozoa (8.9%). Rates of isolation of diarrhoea-associated pathogens were 29% from diarrhoeal stools and 17% from asymptomatic stools (P = 0.01, chi(2) test). The association between diarrhoea and infection with bacteria or protozoa was weak and there was no association with helminths. Cryptosporidium parvum infection alone was associated with low CD4 counts. CONCLUSIONS: Diarrhoea was common and most strongly associated with low CD4 counts. Bacteria were frequently found, even in stools from asymptomatic individuals. Over two-thirds of diarrhoeal episodes were undiagnosed, suggesting that unidentified agents or primary HIV enteropathy are important causes of diarrhoea in this population.

AIDS-Related Opportunistic Infections↗
PubMed2002

Operational assessment of isoniazid prophylaxis in a community AIDS service organisation in Uganda.

SETTING: Isoniazid therapy was shown to be 70% effective at preventing tuberculosis in HIV-infected, PPD-positive Ugandan adults, but the feasibility of implementation outside an efficacy trial has not been established. OBJECTIVE: To study uptake, adherence and feasibility of a 6-month course of isoniazid preventive therapy in community-based HIV clinics in Uganda. DESIGN: Observational cohort study describing selection of patients and adherence to isoniazid 300 mg daily. Adherence was measured by clinic attendance, pill counts and urine isoniazid metabolite testing. Implementation was costed on a service delivery basis. RESULTS: Of 1597 cohort members, 22% were PPD-positive. Over 18 months, 193 PPD-positive individuals were assessed for prophylaxis and 98 (51%) were enrolled. Of those enrolled, 74 (76%) completed their course of isoniazid therapy, and 80% were fully adherent. Symptoms or previous treatment for tuberculosis and suspicion of tuberculous lymphadenopathy were the main reasons for exclusion. The additional cost of providing this service was US $14,549. CONCLUSION: Clinics specialising in the care of persons with HIV/AIDS can successfully implement isoniazid prophylaxis. Difficulties in excluding active tuberculosis and the costs of running the programme may limit its widespread implementation.

AIDS-Related Opportunistic Infections↗
PubMed2001

Man, monkeys and malaria.

Bizarre though it may now seem, in the last century a whole series of experiments was conducted that involved injecting fresh monkey blood into human volunteers or patients. The reasons, valid at the time, were either to treat neurosyphilis with a relatively benign simian malaria infection (so-called pyrogen therapy), or to establish which monkey malaria species were potential zoonotic reservoirs of infection that then may have interfered with malaria eradication campaigns. Although direct inoculation of fresh blood is the most effective way of retroviruses as well as malaria parasites crossing the species barrier, this hypothesis was never taken up or researched. Unlikely, but not disproved, it is important to remember some of the more hazardous experiments that were done in good faith, too long ago to be recorded on electronic databases.

Animals↗
PubMed2001

Cotrimoxazole prophylaxis in adults infected with HIV in low-income countries.

Two recent placebo-controlled trials of cotrimoxazole in HIV-infected adults, conducted by independent groups but in the same city (Abidjan, Côte d'Ivoire), have both shown important positive impacts. One study where cotrimoxazole or placebo was given to tuberculosis-HIV co-infected patients showed a significant reduction in mortality; the second study with a similar protocol, in HIV-infected patients without major co-morbidity at trial entry, showed a significant reduction in morbidity but no effect on mortality. These data have been interpreted by some as conclusive enough to recommend cotrimoxazole for all people with HIV/AIDS in Africa. Others have been more cautious, noting that Abidjan has an atypically low rate of cotrimoxazole resistance among bacterial pathogens, and consider more data are needed before such a sweeping policy decision can be made. Recent data from Senegal showed no benefit but this trial, like several others, was terminated prematurely because the investigators felt it unethical to continue after the Abidjan results were released. The situation is somewhat confused and confusing. This review attempts to put the current debate into context and to review the current position of cotrimoxazole in relation to other primary prophylaxis strategies in Africa.

Adult↗
PubMed2000

An improved algorithm for determining HIV type 1 subtypes in a primary laboratory in Uganda.

A pilot study was undertaken with the objective of developing a simple, economical, and efficient algorithm through which to subtype HIV-1 in a large epidemiological cohort study in Uganda. A peptide enzyme immunoassay (PEIA) employing both V3 and gp41 regions and a heteroduplex mobility assay (HMA) were evaluated in comparison with DNA sequencing. Of 146 samples selected, 115 (79%) were successfully sequenced. Taking sequence data as the "gold standard," other assays were compared with these data. The HMA correctly identified 95 (83%) of the samples, and only 1 sample was wrongly identified. The V3 PEIA alone and in combination with gp41 peptides correctly identified 76 and 78% of the samples, respectively; however, the number of wrongly identified samples was four times less with the combination compared with V3 peptides alone (4 versus 16%). The sensitivity, specificity, and positive and negative predictive values for serotype A and D samples were greater for the combination than V3 peptides alone. We have described a new algorithm to segregate subtypes A and D. This algorithm uses the two peptide assays followed by HMA and then DNA sequencing for untypable samples, giving an accuracy of 95% at a cost of 37 and 21% for consumables compared with subtyping all the samples by HMA or DNA sequencing, respectively. This proposed approach is suitable for epidemiological studies in Uganda and other regions with a predominance of A and D subtypes.

Algorithms↗
PubMed1999

Analysis of Salmonella enterica serotype Typhimurium by phage typing, antimicrobial susceptibility and pulsed-field gel electrophoresis.

Three typing methods commonly used for bacteria--phage typing, antimicrobial susceptibility and pulsed-field gel electrophoresis (PFGE)- were used to characterise 64 Salmonella enterica serotype Typhimurium isolates from individual adult patients from Nairobi, Kenya. The isolates encompassed 11 definitive phage types (DTs), which fell into eight PFGE clusters; 31.3% of isolates were either untypable or reacted nonspecifically with the phages used for typing and 26.6% were of DT 56. Plasmids of c. 100 kb were responsible for self-transferable multiresistance among the isolates. Analysis by PFGE and phage type demonstrated that multiresistant Typhimurium strains causing diarrhoea and invasive disease were multiclonal.

Adult↗
PubMed1999

Genotype analysis of Escherichia coli strains isolated from children and chickens living in close contact.

Escherichia coli isolates from rectal swabs from 62 chickens and stools from 42 children living in close contact with chickens on the same farms in Kiambu district, Kenya, were compared for their genetic relatedness. Antibiotic susceptibility profiles broadly categorized isolates from the children and from the chickens into two separate clusters: the majority (144; 85.5%) of the E. coli isolates from children were multidrug resistant, while the majority (216; 87.1%) of the E. coli isolates from chickens were either fully susceptible or resistant only to tetracycline. Sixty- and 100- to 110-MDA plasmids were found to encode the transferable resistance to co-trimoxazole and tetracycline. HindIII restriction endonuclease digestion of the 60- and 100- to 110-MDA plasmids produced four distinct patterns for isolates from children and three distinct patterns for isolates from chickens. XbaI digestion of genomic DNA followed by pulsed-field gel electrophoresis (PFGE) analysis produced 14 distinct clusters. There were six distinct PFGE clusters among the isolates from children, while among the isolates from chickens there were seven distinct clusters. Only one PFGE cluster contained isolates from both children and chickens, with the isolates displaying an approximately 60% coefficient of similarity. This study showed that although several different genotypes of E. coli were isolated from children and chickens from the same farms, the E. coli strains from these two sources were distinct.

Animals↗
PubMed1999

HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5 and DQB1 polymorphism detected by PCR-SSP in a semi-urban HIV-positive Ugandan population.

PCR-SSP was used to HLA-type a cohort of Ugandan HIV-positive individuals. The results represent a more comprehensive description of HLA in an African population than previously described and are in concordance with data from a general Black population. Substantial differences exist between this population and Caucasoid populations in which immunological responses to HIV have been investigated; this emphasises that the main HLA-restrictive elements for HIV-specific cytotoxic T lymphocytes will most likely be different for each population.

Base Sequence↗
PubMed1997

Comparison of cost effectiveness of directly observed treatment (DOT) and conventionally delivered treatment for tuberculosis: experience from rural South Africa.

OBJECTIVE: To conduct an economic evaluation of directly observed treatment (DOT) and conventionally delivered treatment for the management of new cases of tuberculosis in adults. DESIGN: Community based directly observed treatment, which has been implemented in the Hlabisa district of South Africa since 1991, was compared with a conventional approach to tuberculosis treatment widely used in Africa. Each was assessed in terms of cost, cost effectiveness, and feasibility of implementation within existing resource constraints. SETTING: Hlabisa Health District, South Africa. SUBJECTS: Adult patients with new cases of tuberculosis on smear testing; the number of cases increased from 20 per month to over 100 from 1991 to 1996. MAIN OUTCOME MEASURES: Cost of case management in 1996, cost effectiveness in terms of the cost per case cured, and bed requirements in comparison with bed availability for the 1990, 1993, and 1996 caseload. Costs are expressed in US dollars at values for 1996. RESULTS: Directly observed treatment was 2.8 times cheaper overall than conventional treatment ($740.90 compared with $2047.70) to deliver. Directly observed treatment worked out 2.4-4.2 times more cost effective, costing $890.50 per patient cured compared with either $2095.60 (best case) or $3700.40 (worst case) for conventional treatment. The 1996 caseload of tuberculosis required 47 beds to be dedicated to tuberculosis to implement directly observed treatment, whereas conventionally delivered treatment would have required 160 beds; the current number of beds for tuberculosis treatment in Hlabisa is fixed at 56. CONCLUSIONS: Because of the reduced stay in hospital, directly observed treatment is cheaper, more cost effective, and more feasible than conventional treatment in managing tuberculosis in Hlabisa, given the existing hospital bed capacity and the escalating caseload due to the HIV/AIDS epidemic. Such results may hold elsewhere, and wherever conventional tuberculosis management is practised a switch to directly observed treatment will increase hospital capacity to cope with a growing caseload.

Adult↗
PubMed1996

Serotypes and antibiotic susceptibilities of Streptococcus pneumoniae in Nairobi, Kenya.

Two hundred and sixteen clinically significant isolates of Streptococcus pneumoniae from 138 adult patients attending clinics in Nairobi, Kenya over a 2 year period were characterized by antibiotic sensitivity testing and serotyping. Overall antibiotic resistance rates were: penicillin, 25%; tetracycline, 34%; erythromycin, 0%; chloramphenicol, 0.4%. Minimum inhibitory concentrations (MIC's) of penicillin ranged from < 0.008-0.5 microgram/ml. Determination of penicillin resistance (MIC > or = 0.1 microgram/ml) by oxacillin 1 microgram disc diffusion zone diameter < or = 20 mm was 100% sensitive, 92% specific. Relative resistance to oxacillin (MIC range 0.25-1.0 microgram/ml) accounted for penicillin sensitive isolates determined falsely to be penicillin resistant by oxacillin disc testing. Penicillin resistance was more frequent in sputum isolates at 35% than in blood isolates at 18% (P = 0.013). Serotypes 6, 10, 14, 16, 19 and 23 were associated with penicillin resistance. This study provides information of value for planning management strategies for pneumococcal disease from an area where there are few existing data.

Adult↗
PubMed1996

Bacteriuria in a cohort of predominantly HIV-1 seropositive female commercial sex workers in Nairobi, Kenya.

Although significant bacteriuria and urinary tract infection are more common in immunocompetent women than men, studies linking HIV immunosuppression with an increased risk of developing urinary infection have so far only been carried out in men. We therefore examined the relationship between bacteriuria and HIV status and CD4+cell count in a relatively homogeneous cohort of female commercial sex workers (CSW) attending a community clinic in Nairobi. Two hundred and twenty-two women were enrolled, and grouped according to HIV status and CD4 count. Group 1 were HIV seronegative (n = 52); Group 2 were HIV seropositive with CD4 + counts above 500 x 10(6)/l (n = 51); Group 3 were HIV seropositive with CD4 + counts between 201 and 500 x 10(6)/l (n = 67); Group 4 were HIV seropositive with CD4+counts below 200 x 10(6)/l (n = 52). Clinical signs and symptoms were noted and mid-stream specimens of urine obtained for culture and sensitivity. Overall 23% (50/222) had significant bacteriuria. The rates in each group respectively were 25%, 29%, 19% and 23% and there was no significant association between bacteriuria and HIV status; or between bacteriuria and level of immuno-suppression as indicated by CD4 + count. Overall 19% (30/222) of women had symptoms (frequency; dysuria; loin pain; smelly urine) or signs (fever; loin tenderness) compatible with urinary tract infection. However there was no significant association between symptoms or signs of infection and bacteriuria or HIV status. A typical range of pathogens, predominantly Enterobacteriaceae, were isolated and there were high rates of resistance to commonly used antimicrobials as well as 10% resistance to ciprofloxacin. Although high rates of significant bacteriuria can occur in highly sexually-active women, this appears unrelated to HIV infection or the level of HIV-related immunosuppression and is generally asymptomatic or clinically indistinct.

Adolescent↗
PubMed1996

Multi-drug resistant non-typhi salmonellae in Kenya.

Two methods of plasmid characterization, restriction digest patterns and incompatibility grouping, were used to study self-transmissible multi-drug resistance among non-typhi salmonellae (NTS). Resistance to ampicillin and other commonly applied beta-lactams was evaluated by iso-electric focusing and disc inactivation. Of the NTS isolated from blood, 75% were Salmonella typhimurium but those included several different phage types. Over 47% of isolates were resistant to three or more of the readily available drugs including ampicillin, cefuroxime, chloramphenicol, co-trimoxazole, streptomycin and tetracycline. Self-transferable resistance plasmids (c. 100 kb) were essentially of incompatibility group incFIIA, but their restriction fragment patterns revealed a diversity in relatedness. More than half of parent strains and their transconjugants produced beta-lactamases which co-electrophoresed with TEM-1 and OXA-1. This study has observed a disturbingly high prevalence of transmissible multi-drug resistance among NTS which are an important cause of morbidity in HIV-1 seropositive individuals.

Ampicillin Resistance↗
PubMed1995

Nasopharyngeal carriage of Staphylococcus aureus and carriage of tetracycline-resistant strains associated with HIV-seropositivity.

The aim of this prospective study was to investigate the relationship between carriage of antibiotic-resistant Staphylococcus aureus and infection with the human immunodeficiency virus (HIV). A total of 554 pernasal swabs was taken during a six-month period from 554 adult patients attending three outpatient clinics and from inpatients from a hospital in Nairobi, Kenya. Overall, 121 swabs (22%) yielded Staphylococcus aureus, there being significantly higher carriage in HIV-positive patients (71/264, 27%) than in HIV-negative patients (50/290, 17%); p = 0.008. Antimicrobial resistance rates were determined for 110 isolates and were high for penicillin (91%) and tetracycline (72%) and low for erythromycin (8%), methicillin (3%), gentamicin (5%) and chloramphenicol (0%). Genetic analysis showed plasmids in the range of 24-42 MDa to be associated with beta-lactamase production and plasmids in the range of 3-5 MDa to be associated with resistance to tetracycline, erythromycin and trimethoprim. All nine erythromycin-resistant strains were from HIV-positive patients (p = 0.02). There was a significant association of tetracycline resistance with HIV seropositivity (p = 0.002). The association of HIV seropositivity with Staphylococcus aureus carriage and carriage of antibiotic-resistant strains against the background of the HIV epidemic are of relevance in individual patient care and raise concern for public health.

Adult↗