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Ifedayo M Adetifa,
Martin O C Ota,
David Jeffries,
Moses Lugos,
Abdulrahman Hammond,
Nicholas Battersby,
Patrick Owiafe,
Simon Donkor,
Martin Antonio,
Hannah Ibanga,
Roger Brookes,
Peter Aka,
Robert Walton, Richard Adegbola,
Philip Hill
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ABSTRACT: Rationale Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required. Objectives To measure Isoniazid induced qualitative and quantitative reversion of positive ESAT-6 and CFP-10 (EC) Interferon gamma ELISPOT tests in LTBI. Methods This was a randomized, blinded and placebo controlled trial of Isoniazid (INH) in ESAT-6 and CFP-10 (EC) ELISPOT and Mantoux test positive participants. Measurements and Main Results Participants received a 6-month course of 900mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tests for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6, between treatment arms were compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model fitted using the R package cplm to allow for zero inflation and over dispersion of qualitative response. This trial was registered with ClinicalTrials.gov (NCT00130325). The proportions of EC ELISPOT positive subjects reduced over time (p <0.001) but did not differ by study arm (p=0.36). Median spot forming units (SFUs) for ESAT-6 and CFP-10 also declined significantly with time (p<0.001) but did not differ by study arm (p=0.74 and 0.71 respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time. Conclusions In contacts with LTBI, Isoniazid therapy plays no role in observed decreases in M. tuberculosis antigen-specific T-cell responses over time. Interferon gamma ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI.
American Journal of Respiratory and Critical Care Medicine 12/2012; · 11.08 Impact Factor
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Digna R Velez Edwards,
Alessandra Tacconelli,
Christian Wejse,
Philip C Hill,
Gerard A J Morris,
Todd L Edwards,
John R Gilbert,
Jamie L Myers,
Yo Son Park,
Martin E Stryjewski,
Eduardo Abbate,
Rosa Estevan,
Paulo Rabna,
Giuseppe Novelli,
Carol D Hamilton, Richard Adegbola,
Lars Østergaar,
Scott M Williams,
William K Scott,
Giorgio Sirugo
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ABSTRACT: The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (-2581A/G), rs2857656 (-362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility.
PLoS ONE 01/2012; 7(2):e32275. · 4.09 Impact Factor
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ABSTRACT: Abstract Background Frozen storage often precedes metagenomic analysis of biological samples; however, the freezing process can have adverse effects on microbial composition. The effect of freezing on the detection of bacteria inhabiting the infant nasopharynx, a major reservoir of bacterial pathogens, was investigated. Methods 16S ribosomal RNA (rRNA) gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis of nasopharyngeal (NP) swabs from twelve Gambian infants was employed. NP swabs were analysed within hours of collection and then after 30 days of storage at -70°C. Results There was substantial heterogeneity among subjects with respect to the effect of freezing on the number of operational taxonomic units (OTUs) detected. Nevertheless, the mean number of OTUs decreased after frozen storage and the relative abundance for 72% of the OTUs changed by less than 0.5% after deep frozen storage. There were differences in the odds of detection and relative abundance of OTUs matched with Moraxella sp., Haemophilus sp./Burkholderia sp., and Pseudomonas sp. A strong interaction between sex and the effect of freezing was found, whereby there was no significant change observed for males while the mean number of OTUs significantly declined among female infants following frozen storage. Conclusions Although frozen storage of biological samples is often necessary for archiving and logistic purposes, the potential effects on the number of taxa (composition) detected in microbial community studies are significant and should not be overlooked. Moreover, genetic factors such as sex may influence the integrity of nucleic acids during the freezing process.
BMC Clinical Pathology. 01/2011;
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Gerard A J Morris,
Digna R Velez Edwards,
Philip C Hill,
Christian Wejse,
Cyrille Bisseye,
Rikke Olesen,
Todd L Edwards,
John R Gilbert,
Jamie L Myers,
Martin E Stryjewski, [......],
Alessandra Tacconelli,
Giuseppe Novelli,
Ercole Brunetti,
Peter Aaby,
Morten Sodemann,
Lars Østergaard, Richard Adegbola,
Scott M Williams,
William K Scott,
Giorgio Sirugo
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ABSTRACT: We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3' UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58-1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.
PLoS ONE 01/2011; 6(2):e16656. · 4.09 Impact Factor
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Gerard A J Morris,
Digna R Velez Edwards,
Philip C Hill,
Christian Wejse,
Cyrille Bisseye,
Rikke Olesen,
Todd L Edwards,
John R Gilbert,
Jamie L Myers,
Martin E Stryjewski, [......],
Alessandra Tacconelli,
Giuseppe Novelli,
Ercole Brunetti,
Peter Aaby,
Morten Sodemann,
Lars Ostergaard, Richard Adegbola,
Scott M Williams,
William K Scott,
Giorgio Sirugo
PLoS ONE 01/2011; 6(2). · 4.09 Impact Factor
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ABSTRACT: The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae; it affects complement resistance and shields the bacterium from phagocytes. Certain capsular serotypes appear to be better able to cause invasive disease than others. Serotypes 1 and 5 are common causes of invasive disease but are rarely isolated from healthy carriers, whereas serotypes 6B and 23F are more frequently isolated from carriage than invasive disease. We have recently shown that serotypes 6B and 19F differ in resistance to complement C3 deposition and opsonophagocytic killing. In this study we assessed the complement resistance and susceptibility to opsonophagocytosis of several other serotypes targeted by the pneumococcal conjugate vaccines. Clinical isolates of serotypes 1, 4, 5, 14, 18C, and 23F were tested along reference strains of corresponding capsular types. The concentration of anticapsular antibodies required for opsonophagocytic killing correlated inversely with C3 deposition on the serotype. Serotype 1 was the most resistant of the clinical isolates to C3 deposition and, along with serotypes 5 and 19F, required the highest concentration of capsule antibodies for opsonophagocytic killing, whereas serotype 23F was the most sensitive to opsonophagocytosis. Sensitivity to C3 deposition and opsonophagocytosis was associated with serotype-specific mortality of invasive pneumococcal disease, suggesting that the primary pathogens, such as serotypes 1 and 5, are more resistant to complement and require a higher concentration of capsule antibodies for opsonophagocytic killing than the opportunistic serotypes such as 6B and 23F, which are associated with a more severe disease outcome.
Infection and immunity 12/2010; 78(12):5252-61. · 4.21 Impact Factor
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Daniel M Weinberger,
Zitta B Harboe,
Elisabeth A M Sanders,
Moses Ndiritu,
Keith P Klugman,
Simon Rückinger,
Ron Dagan, Richard Adegbola,
Felicity Cutts,
Hope L Johnson,
Katherine L O'Brien,
J Anthony Scott,
Marc Lipsitch
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ABSTRACT: The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness, and disease incidence. There has been some debate, though, regarding whether serotype independently affects the outcome of invasive pneumococcal disease (IPD). Published studies have shown variable results with regard to case-fatality ratios for specific serotypes and the role of host factors in affecting these relationships. We evaluated whether risk of death due to IPD is a stable serotype-associated property across studies and then compared the pooled effect estimates with epidemiologic and biological correlates.
We performed a systematic review and meta-analysis of serotype-specific disease outcomes for patients with pneumonia and meningitis. Study-specific estimates of risk of death (risk ratio [RR]) were pooled from 9 studies that provided serotype-specific data on pneumonia and meningitis using a random-effects method with serotype 14 as the reference. Pooled RRs were compared with RRs from adults with low comorbidity scores to evaluate potential confounding by host factors.
Significant differences were found in the RR estimates among serotypes in patients with bacteremic pneumonia. Overall, serotypes 1, 7F, and 8 were associated with decreased RRs, and serotypes 3, 6A, 6B, 9N, and 19F were associated with increased RRs. Outcomes among meningitis patients did not differ significantly among serotypes. Serotypes with increased RRs had a high carriage prevalence, had low invasiveness, and were more heavily encapsulated in vitro.
These results suggest that IPD outcome, like other epidemiologic measures, is a stable serotype-associated property.
Clinical Infectious Diseases 09/2010; 51(6):692-9. · 9.15 Impact Factor
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ABSTRACT: Abstract
Background
Currently available tools cannot be used to distinguish between sub-species of the M. tuberculosis complex causing latent tuberculosis (TB) infection. M. africanum causes up to half of TB in West- Africa and its relatively lower progression to disease suggests the presence of a large reservoir of latent infection relative to M. tuberculosis .
Methods
We assessed the immunogenicity of the TbD1 region, present in M. africanum and absent from "modern" M. tuberculosis , in an ELISPOT assay using cells from confirmed M. africanum or M. tuberculosis infected TB patients without HIV infection in the Gambia.
Results
Antigens from the TbD1 region induced IFNγ responses in only 35% patients and did not discriminate between patients infected with M. africanum vs. M. tuberculosis , while PPD induced universally high responses.
Conclusions
Further studies will need to assess other antigens unique to M. africanum that may induce discriminatory immune responses.
BMC Infectious Diseases. 01/2010;
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Gillian F Black,
Bonnie A Thiel,
Martin O Ota,
Shreemanta K Parida, Richard Adegbola,
W Henry Boom,
Hazel M Dockrell,
Kees L M C Franken,
Annemiek H Friggen,
Philip C Hill,
Michel R Klein,
Maeve K Lalor,
Harriet Mayanja,
Gary Schoolnik,
Kim Stanley,
Karin Weldingh,
Stefan H E Kaufmann,
Gerhard Walzl,
Tom H M Ottenhoff
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ABSTRACT: Increasing knowledge about DosR regulon-encoded proteins has led us to produce novel Mycobacterium tuberculosis antigens for immunogenicity testing in human populations in three countries in Africa to which tuberculosis (TB) is endemic. A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human immunodeficiency virus-negative adult household contacts of active pulmonary TB cases from South Africa (n = 56), The Gambia (n = 26), and Uganda (n = 49) were tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked responses in >75% of study participants in all three countries. Of the DosR regulon-encoded antigens tested, Rv1733c was the most commonly recognized by participants from both South Africa and Uganda and the third most commonly recognized antigen in The Gambia. The four most frequently recognized DosR regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) included the three most immunogenic antigens in South Africa. In contrast, Rv3131 induced the highest percentage of responders in Gambian contacts (38%), compared to only 3.4% of Ugandan contacts and no South African contacts. Appreciable percentages of TB contacts with a high likelihood of latent M. tuberculosis infection responded to several novel DosR regulon-encoded M. tuberculosis proteins. In addition to significant similarities in antigen recognition profiles between the three African population groups, there were also disparities, which may stem from genetic differences between both pathogen and host populations. Our findings have implications for the selection of potential TB vaccine candidates and for determining biosignatures of latent M. tuberculosis infection, active TB disease, and protective immunity.
Clinical and vaccine immunology: CVI 06/2009; 16(8):1203-12. · 2.37 Impact Factor
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ABSTRACT: Nasopharyngeal carriage of Streptococcus pneumoniae is extremely prevalent in The Gambia. We studied the effects of vaccination with pneumococcal conjugate vaccines on the carriage of individual serotypes and on antimicrobial resistance in vaccinated children and their younger siblings.
A longitudinal study of a subsample of children (n=2342) who participated in a randomized, placebo controlled trial of a 9-valent pneumococcal conjugate vaccines (PCV-9) in The Gambia, and a cross-sectional study of non-PCV-9-vaccinated younger siblings (n=675).
Recipients of PCV-9 were less likely to carry vaccine serotypes 4, 6B, 9V, 14, 19F, and 23F but more likely to carry vaccine-associated 19A and 9 nonvaccine serotypes at approximately 6 months postvaccination (age, 12 months) than were controls (each P<0.05). At approximately 16 months postvaccination, carriage of vaccine-associated-serotype 6A was also significantly reduced (P<0.01) while 3 other nonvaccine serotypes were more prevalent in the PCV-9 recipients (each P<0.05). At 16 months, but not 6 months, postvaccination PCV-9 recipients had lower rate of carrying isolates resistant to tetracycline and trimethoprim-sulfamethoxazole (TMP-SMZ) than controls (risk ratio: 0.90 and 0.95, respectively; each P<0.05). There was no difference in patterns of carriage of pneumococci in younger siblings of PCV-9 or placebo recipients.
The effects of 9-valent pneumococcal conjugate vaccines on carriage of pneumococci persisted for at least 16 months postvaccination in Gambian children. Vaccination had no indirect effect on carriage in younger siblings and there was limited impact on antibiotic resistance.
The Pediatric Infectious Disease Journal 06/2009; 28(11):990-5. · 3.58 Impact Factor
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ABSTRACT: We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively.
Annals of Clinical Microbiology and Antimicrobials 02/2009; 8:3. · 2.64 Impact Factor
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Martin Antonio,
Ishrat Hakeem,
Timothy Awine,
Ousman Secka,
Kawsu Sankareh,
David Nsekpong,
George Lahai,
Abiodun Akisanya,
Uzochukwu Egere,
Godwin Enwere,
Syed M A Zaman,
Philip C Hill,
Tumani Corrah,
Felicity Cutts,
Brian M Greenwood, Richard A Adegbola
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ABSTRACT: Streptococcus pneumoniae serotype 1 causes > 20% of invasive disease, among all age groups combined, in The Gambia. In contrast, it is rarely detected in carriage studies. This study compares the molecular epidemiology of S. pneumoniae serotype 1 causing invasive disease in The Gambia between 1996 and 2005 to those carried in the nasopharynx between 2004 and 2006.
A total of 127 invasive and 36 nasopharyngeal carriage serotype 1 isolates were recovered from individuals of all age groups and were analyzed by serotyping, antibiotic susceptibility testing and MLST. MLST analysis revealed 23 different sequence types (STs), 18 of which were novel. The most prevalent clone among the 163 isolates was ST618 (70.5%), followed by ST3575 (7.4%), ST2084 (2.5%) and ST612 (2.5%). A single ST (ST618), previously shown to belong to the ST217 hypervirulent clonal complex, was frequent among carriage (61.1%) and invasive (72.7%) serotype 1 isolates. ST618 causing both paediatric and adult disease peaked annually in the hot dry season and caused outbreak in 1997 and 2002.
For over a decade, isolates of ST618 have been the dominant lineage among serotype 1 carriage and disease isolates circulating in the Gambia. This lineage shows similar epidemiological features to those of the meningococcus in the African meningitis belt being able to cause outbreaks of disease.
BMC Microbiology 11/2008; 8:198. · 3.04 Impact Factor
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ABSTRACT: To assess the effect of vaccines against pneumonia in Gambian children.
Data from a randomized, controlled trial of a 9-valent pneumococcal conjugate vaccine (PCV) were used. Radiographic findings, interpreted using WHO definitions, were classified as primary end point pneumonia, 'other infiltrates/abnormalities' pneumonia and pneumonia with no abnormality. We calculated the incidence of the different types of radiological pneumonia, and compared clinical and laboratory features between these groups.
Among children who did not receive PCV, the incidence of pneumonia with no radiographic abnormality was about twice that of 'other infiltrates' pneumonia and three times that of primary endpoint pneumonia. Most respiratory symptoms, reduced feeding and vomiting occurred most frequently in children with primary endpoint pneumonia. These children were more likely to be malnourished, to have bronchial breath sounds or invasive bacterial diseases, and to die within 28 days of consultation than children in the other groups. Conversely, a history of convulsion, diarrhoea or fast breathing, malaria parasitaemia and isolation of salmonellae were commoner in children with pneumonia with no radiographic abnormality. Lower chest wall indrawing and rhonchi on auscultation were seen most frequently in children with 'other infiltrates/abnormalities' pneumonia.
Primary endpoint pneumonia is strongly associated with bacterial aetiology and severe pneumonia. Since this category of pneumonia is significantly reduced after vaccination with Hib and pneumococcal vaccines, the risk-benefit of antimicrobial prescription for clinical pneumonia for children with increased respiratory rate may warrant re-examination once these vaccines are in widespread use.
Tropical Medicine & International Health 12/2007; 12(11):1377-85. · 2.80 Impact Factor
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American Journal of Clinical Nutrition 02/2007; 85(1):242-3; author reply 243. · 6.67 Impact Factor
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Philip Hill,
Charles Onyeama,
Usman Ikumapayi,
Ousman Secka,
Samuel Ameyaw,
Naomi Simmonds,
Simon Donkor,
Stephen Howie,
Mary Tapgun,
Tumani Corrah, Richard Adegbola
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ABSTRACT: Abstract
Background
Few studies on bacteraemia in Africa have been published. We aimed to prospectively identify the causative organisms of bacteraemia in The Gambia and their relation to clinical diagnoses, outcome and antimicrobial susceptibility.
Methods
Between November 2003 and February 2005 we studied those admitted to the Medical Research Council hospital who were suspected of having bacteraemia. We documented clinical features, outcome, pathogens identified and their susceptibility patterns, and searched for factors associated with bacteraemia.
Results
871 patients were admitted and had a blood culture taken. The median age was 2 years (range 2 months to 80 years) and 36 of 119 tested were HIV positive; 54.5% were male. 297 (34%) had a positive result and 93 (10.7% overall) were considered a genuine pathogen. Those with bacteraemia were more likely to die in hospital (OR 2.79; 1.17–6.65, p = 0.017) and to have a high white cell count (WCC; OR 1.81;95% CI 1.09–3.02; p = 0.022). Three organisms accounted for 73% of bacteraemias: Streptococcus pneumoniae (45.2%), Staphylococcus aureus (18.3%) and Escherichia coli (9.7%) while non-typhoidal salmonellae (NTS) accounted for 8.6%. Antimicrobial susceptibility of S. pneumoniae was very high to penicillin (97.5%); high resistance was found to co-trimoxazole. S. aureus was generally highly susceptible to cloxacillin, gentamicin and chloramphenicol. E. coli and NTS were all susceptible to ciprofloxacin and mostly susceptible to gentamicin. Thirteen (33%) S. pneumoniae isolates were of serotypes contained in a 7-valent pneumococcal conjugate vaccine and 20 (51.3%) were of the same serogroup.
Conclusion
In The Gambia, those with bacteraemia are more likely than those without to die in hospital and to have a raised peripheral blood WCC. S. pneumoniae is the most common organism isolated. Introduction of a pneumococcal conjugate vaccine can be expected to lead to a reduction in disease incidence.
BMC Infectious Diseases. 01/2007;
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ABSTRACT: Abstract
Background
IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Their performance may depend on assay format and may vary across populations and settings. We compared the diagnostic performance of an in-house T -cell and commercial whole blood-based IGRAs for the diagnosis of LTBI and TB disease in The Gambia.
Methods
Newly diagnosed sputum smear positive cases and their household contacts were recruited. Cases and contacts were bled for IGRA and contacts had a Mantoux skin test. We assessed agreement and discordance between the tests and categorized a contact's level of M. tuberculosis exposure according to where s/he slept relative to a case: the same room, same house or a different house. We assessed the relationship between exposure and test results by multiple logistic regression.
Results
In 80 newly diagnosed TB cases, the sensitivity of ELISPOT was 78.7% and for QFT-GIT was 64.0% (p = 0.047). Of 194 household contacts 57.1% and 58.8% were positive for ELISPOT and QFT-GIT respectively. The overall agreement between both IGRAs for LTBI in contacts was 71.4% and there was no significant discordance (p = 0.29). There was significant discordance between the IGRAs and TST. Neither IGRA nor TST had evidence of false positive results because of Bacille Calmette Guérin (BCG) vaccination. However, agreement between QFT-GIT and TST as well as discordance between both IGRAs and TST were associated with BCG vaccination. Both IGRAs responded to the M. tuberculosis exposure gradient and were positively associated with increasing TST induration (p = 0.003 for ELISPOT and p = 0.001 for QFT-GIT).
Conclusion
The ELISPOT test is more sensitive than the QFT-GIT for diagnosing TB disease. The two tests perform similarly in the diagnosis of LTBI in TB contacts. Significant discordance between the two IGRAs and between each and the TST remain largely unexplained.
BMC Infectious Diseases. 01/2007;
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ABSTRACT: The incidence of community-acquired bacteremia (CAB) in Africa is several-fold higher than in industrialized countries. We report here the incidence of invasive bacterial infections in rural Gambia and compare the clinical characteristics of children with pneumococcal infection with those of children with extraintestinal nontyphoidal salmonella infection (NTS) or other bacterial infections.
As part of a pneumococcal conjugate vaccine trial, we investigated children aged 2-29 months who presented with signs suggestive of invasive bacterial infections.
The incidence of invasive bacterial infections in all subjects was 1009 (95% CI, 903-1124) cases per 100,000 person-years. It was 1108 (95% CI, 953-1282) among children who had not received pneumococcal conjugate vaccine. Incidence decreased with increasing age but remained relatively high in 24- to 29-month-olds for pneumococcal infections. Pneumococcal infection was more frequent than NTS infections in the hot dry season. Respiratory symptoms and signs, consolidation on chest radiograph, and a primary diagnosis of pneumonia were more frequent in children with pneumococcal infection than in those with NTS or other infections. Diarrhea, laboratory evidence of malaria infection, and a primary diagnosis of malaria were more common in children with NTS infections.
Bacterial infections continue to cause significant morbidity in rural Africa. Although vaccines could greatly reduce the pneumococcal burden, a high index of suspicion and appropriate use of antimicrobials are needed to manage other causes of invasive bacterial infections.
The Pediatric Infectious Disease Journal 09/2006; 25(8):700-5. · 3.58 Impact Factor
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ABSTRACT: Abstract
Background
New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis- specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment.
Methods
We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation.
Results
We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 × 10<sup>5 </sup>cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months.
Conclusion
Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis -specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted.
BMC Infectious Diseases. 01/2006;
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ABSTRACT: Abstract
Background
The tuberculosis (TB) epidemic in Africa is on the rise, even in low-HIV prevalence settings. Few studies have attempted to identify possible reasons for this. We aimed to identify risk factors for pulmonary tuberculosis in those attending a general outpatients clinic in The Gambia, a sub-Saharan African country with relatively low HIV prevalence in the community and in TB patients.
Methods
We conducted a case control study at the Medical Research Council Outpatients' clinic in The Gambia. Pulmonary TB cases were at least 15 years old, controls were age and sex matched clinic attendees. Participants were interviewed using a structured questionnaire.
Results
100 sputum smear positive TB cases and 200 clinic controls were recruited. HIV prevalence was 6.1% in cases and 3.3% in controls. Multivariable assessment of host factors showed that risk of TB was increased among the Jola ethnic group and smokers, and decreased in those in a professional occupation. Assessment of environmental factors showed an increased risk with household crowding, history of household exposure to a known TB case, and absence of a ceiling in the house. In a combined multivariable host-environment model, the risk of TB increased with crowding, exposure to a known TB case, as well as amongst the Jola ethnic group.
Conclusion
In The Gambia, household crowding and past household exposure to a known TB case are the standout risk factors for TB disease. Further research is needed to identify why risk of TB seems to differ according to ethnicity.
BMC Public Health. 01/2006;
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The Lancet 366(9481):199-200. · 38.28 Impact Factor
