Pius Agbenorku

Comparative Study of the Sensitivity of Different Diagnostic Methods for the Laboratory Diagnosis of Buruli Ulcer Disease

BACKGROUND Several diagnostic laboratory methods are available for case confirmation of Buruli ulcer disease. This study assessed the sensitivity of various diagnostic tests in relation to clinical presentation of the disease, type of diagnostic specimen, and treatment history. METHODS Swab samples, 3-mm punch biopsy tissue specimens, and surgically excised tissue specimens from 384 individuals with suspected Buruli ulcer disease were obtained at 9 different study sites in Ghana and were evaluated with dry reagent-based polymerase chain reaction (PCR), microscopic examination, culture, and histopathological analysis. The study subjects presented with nonulcerative and ulcerative lesions and were divided into 3 treatment groups: (1) previously untreated patients scheduled for antimycobacterial treatment, (2) patients treated with surgery alone, and (3) patients treated with surgery in combination with previous antimycobacterial treatment. RESULTS Of 384 suspected cases of Buruli ulcer disease, 268 were confirmed by at least 1 positive test result. The overall sensitivity of PCR (85%) was significantly higher than that of microscopic examination (57%) and culture (51%). After data were stratified by treatment group, type of lesion, and diagnostic specimen type, analysis revealed that PCR of 3-mm punch biopsy tissue specimens (obtained from previously untreated nonulcerative lesions) and of swab samples (obtained from previously untreated ulcers) had the highest diagnostic sensitivity (94% and 90%, respectively). Although duration of the disease did not significantly influence the sensitivity of any test, previous antimycobacterial treatment was significantly associated with decreased sensitivity of PCR and culture. CONCLUSIONS Across all subgroups, PCR had the highest sensitivity. PCR assessment of 3-mm punch biopsy tissue specimens proved to be the best diagnostic tool for nonulcerative lesions, and PCR assessment of swab samples was the best diagnostic tool for ulcerative lesions. For monitoring of antimycobacterial treatment success within controlled trials, however, only culture is appropriate.

Cleft lip and palate surgery in Kumasi, Ghana: 2001-2005.

Background: A retrospective review of cleft lip operations at our hospital during 1991-2000 showed that on average 17 patients per year were operated on for cleft lip and palate and that each year saw an increasing number of patients being treated. The purpose of this study was to determine the change that had occurred in the number of patients treated for cleft lip and palate during the five-year period from 2001-2005. Patients and Methods: This is a retrospective review of cleft lip and palate operations carried out under general anesthesia at the Komfo Anokye Teaching Hospital. Operating room records were the source of data. Patients treated under local anesthesia were excluded. Information collected included age, gender, and diagnosis. The results were displayed in tables and graphs. Results: A total of 344 patients were operated for cleft lip and palate during the five-year period, i.e. 69 operations per year. The patients comprised 58% males and 42% females and ranged in age from 1 month to 32 years with a mean age of 3.9 years. Unilateral cleft lip operations constituted 78% of all operations. Each succeeding year saw an increase in the number of operations being carried out year during the five-year period. Conclusion: The marked increase in the number of cleft operations per year in our hospital during the period under study was probably due to greater awareness in the community; free surgeries provided by local surgeons with financial support from a US-based NGO; and free operations by a visiting surgical team. Financial, logistical and training support to cleft teams in developing countries is likely to lead to more surgeries for children with cleft.

A Genotypic Approach for Detection, Identification, and Characterization of Drug Resistance in Mycobacterium ulcerans in Clinical Samples and Isolates from Ghana

Standardized antimycobacterial therapy is considered the treatment of choice for Buruli ulcer disease. To assess the prevalence of drug resistance among clinical Mycobacterium ulcerans isolates in Ghana, we conducted a sequence-based approach to detect mutations associated with drug resistance. We subjected clinical samples to direct DNA sequencing of rpoB and rpsL genes and compared culture and whole-genome extracts regarding the efficiency of sequence analysis; 99.1% (rpoB) and 100% (rpsL) of the patients harbored M. ulcerans wild type. In one isolate (0.9%), a point mutation of the rpoB gene at codon Ser522 leading to an amino acid change was detected. Culture extracts yielded a significantly higher sequencing efficiency than whole-genome extracts. Our data suggest a low level of drug resistance in Ghana. However, mutations associated with drug resistance do occur and require monitoring. Improved techniques are necessary to enhance the efficiency of sequence analysis of whole-genome extracts.

Factors enhancing the control of Buruli ulcer in the Bomfa communities, Ghana

This study examines factors that may enhance the control and holistic treatment of Buruli ulcer in an endemic area of the Ashanti Region in Ghana. A total of 189 Buruli ulcer patients from the Bomfa sub-district were treated at the Global Evangelical Mission Hospital, Apromase-Ashanti, Ghana, from January to December 2005. Diagnosis was based on clinical findings and confirmed by any two positives of Ziehl-Neelson test for acid fast bacilli, polymerase chain reaction and histopathology. Children up to age 14 made up 43.4% of the cases; male: female ratio was 3:2. The mean duration of hospitalization was 77 days and hospital stay was significantly correlated with the time spent at home with the disease prior to admission; also, 76.7% of the cases were late ulcers. Of the 189 patients, 145 (i.e. 76.7%) were treated with antibiotics and surgery which involved excision, skin grafting with or without contracture release. A follow-up survey after the introduction of the psychosocial approach recorded fewer (85) new Buruli ulcer (BU) cases of which, the majority (78.8%, 67) were nodules and only 21.2% (18) were ulcers. Health education plays a major role in the holistic treatment of BU. This paper proposes a further study in other endemic areas on the treatment of BU with emphasis on psychosocial approach for holistic treatment.

Multicenter study of wound healing in neurofibromatosis and neurofibroma.

Based on clinical experience, the senior author has become convinced that wounds produced to correct the deformities of patients with neurofibromatosis (NF-1) have produced remarkably good scars, the interesting feature being that progression to keloid or hypertrophic scar is rare. The other point noted was that this situation did not change, no matter the patients race or skin color. There have been few reports describing or discussing this hypothesis. The purpose of this study was to investigate whether wounds produced in the patients with NF-1 produce keloid or hypertrophic scars. The patients with solitary neurofibroma were also included in this study; these were compared with the NF-1 group. This was conducted as a multicenter study. Patients with neurofibromatosis/solitary neurofibroma, who were operated on from 1990 to 2000, were evaluated by reviewing their medical charts and photographs retrospectively. The patients were treated in centers from five different countries. The analysis was undertaken based on the following points: 1) age and sex at surgery; 2) race of the patients; 3) past and family histories of hypertrophic scar and keloid; 4) surgical site(s); 5) diagnosis, NF1 or solitary neurofibroma; 6) surgical complications; 7) number of reoperations to manage the complications; 8) adjuvant therapy for the tumor; 9) depth of the tumors; and 10) incidence of malignant degeneration. A total of 101 cases with neurofibromatosis or solitary neurofibroma was analyzed. The age at surgery ranged from 1 year 6 months to 74 years; sex ratio was 47 males and 54 females. The racial distribution of the patients was 13 white, 13 black, 3 Hispanic, and 58 Asian. There was no past or family history of hypertrophic scar or keloid. The surgical sites were head and neck in 70 cases, trunk in 20 cases, upper extremities in 22 cases, and lower extremities in 20 cases. The clinical diagnosis was NF-1 in 57 cases, solitary neurofibroma in 35 cases, plexiform neurofibroma in four cases, and no distinct clinical diagnosis in five cases. There were no other types of neurofibromatosis. Hematoma and white wide scar were the main postoperative complications found in six cases of NF-1. Infection was also noted in four cases. However, no patient developed hypertrophic scar or keloid in the neurofibromatosis group, whereas two cases showed hypertrophic scar in the solitary neurofibroma group. The outcome showed that the patients with NF-1 and plexiform neurofibroma, no matter the racial group, produce good scars without keloid or hypertrophic changes, whereas solitary neurofibroma has a potential to cause hypertrophic scar.

Burn disasters in the middle belt of Ghana from 2007 to 2008 and their consequences

AIM To study the survival and mortality trends in four fire disasters in the middle belt of Ghana from 2007 to 2008 and to explore measures that could minimize the risk of future disasters. METHODS Data were collected from clinical records from the Burns Intensive Care Unit and the Casualty Unit of the Komfo Anokye Teaching Hospital, Kumasi, Ghana and from the various disaster sites and the Ghana Police Service. RESULTS A total of 212 were injured from four burn disasters; 37 (17%) died on the spot; 175 (83%) reported to the Casualty Unit out of which 46 (26%) were admitted. The victims admitted had mean age 24.6 years with male to female ratio 2.3:1; 25 (54%) of the admitted victims died. The average burned surface area of the admitted victims was 63%, with a mean survival rate of 46%. Statistical analysis for mortality when the surface area of the burn was >70% was 0.0005 (P-value). CONCLUSION The four petrol-related fire disasters showed variable mortality rates. Death and severe disability of victims of future disasters can be avoided if intensive road accident preventive measures and massive public education are encouraged.

District-level hospital trauma care audit filters: Delphi technique for defining context-appropriate indicators for quality improvement initiative evaluation in developing countries.

INTRODUCTION Prospective clinical audit of trauma care improves outcomes for the injured in high-income countries (HICs). However, equivalent, context-appropriate audit filters for use in low- and middle-income country (LMIC) district-level hospitals have not been well established. We aimed to develop context-appropriate trauma care audit filters for district-level hospitals in Ghana, was well as other LMICs more broadly. METHODS Consensus on trauma care audit filters was built between twenty panellists using a Delphi technique with four anonymous, iterative surveys designed to elicit: (i) trauma care processes to be measured; (ii) important features of audit filters for the district-level hospital setting; and (iii) potentially useful filters. Filters were ranked on a scale from 0 to 10 (10 being very useful). Consensus was measured with average percent majority opinion (APMO) cut-off rate. Target consensus was defined a priori as: a median rank of ≥9 for each filter and an APMO cut-off rate of ≥0.8. RESULTS Panellists agreed on trauma care processes to target (e.g. triage, phases of trauma assessment, early referral if needed) and specific features of filters for district-level hospital use (e.g. simplicity, unassuming of resource capacity). APMO cut-off rate increased successively: Round 1--0.58; Round 2--0.66; Round 3--0.76; and Round 4--0.82. After Round 4, target consensus on 22 trauma care and referral-specific filters was reached. Example filters include: triage--vital signs are recorded within 15 min of arrival (must include breathing assessment, heart rate, blood pressure, oxygen saturation if available); circulation--a large bore IV was placed within 15 min of patient arrival; referral--if referral is activated, the referring clinician and receiving facility communicate by phone or radio prior to transfer. CONCLUSION This study proposes trauma care audit filters appropriate for LMIC district-level hospitals. Given the successes of similar filters in HICs and obstetric care filters in LMICs, the collection and reporting of prospective trauma care audit filters may be an important step towards improving care for the injured at district-level hospitals in LMICs.

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10−3), 8q24 (rs987525, P = 1.22 × 10−3), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29. In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

Assessment of mortality prediction models in a Ghanaian burn population

PURPOSE Over 40 new or modified outcome prediction models have been developed for severe burns; with age, total burned surface area (TBSA) and inhalation area as major determinants of mortality. The objective of this study was to assess their applicability in a developing country. PROCEDURES Data were collected retrospectively of a consecutive series of 261 patients (2009-2011) admitted to a Burns Intensive Care. Five outcome prediction models based on admission criteria were evaluated: Bull grid, Abbreviated Burn Severity Index--ABSI, Ryan-model, Belgian Outcome in Burn Injury--BOBI and revised Baux. Discriminative power and goodness-of-fit were assessed by receiver operating characteristic analyses (area under the curve--AUC) and Hosmer-Lemeshow tests. FINDINGS Median age was 10.5 years (IQR: 2.5-27 years), median TBSA 21% (IQR: 11-34%); 55.2% were male, 28 patients died (10.7%). Only 2 patients were intubated (0.8%). The AUC were between 77 and 86%. The ABSI model showed the best calibration (28.7 expected deaths). Ryan, BOBI and rBaux significantly underestimated mortality, whereas Bull showed an overestimation. CONCLUSION This study on a young group of burn patients showed moderate to good discriminative power using all five prediction models. The expected number of deaths tended to be underestimated in the three most recent prediction models.

Buruli Ulcer: Treatment Challenges at Three Centres in Ghana

Aims. This retrospective study was to identify some challenges in the treatment of Buruli ulcer (BU) and present a proposed treatment regime. Materials and Methods. Information from patients medical records, hospital database, and follow-up findings on BU treatment procedures from 1994 to 1998 and from 2004 to 2007 at three research sites in Ghana were reviewed to determine the treatment challenges encountered. Data needed were recorded and analyzed, and results presented using SPSS version 17.0. Results. A total of 489 BU patients information was selected for the study. A majority (56.90%, n = 278) of the patients were children (0–14 years), with a mean age of 12.8 years. Significant challenges in BU treatment in Ghana identified included sequelae (P = 0.041 ), delayed treatment (P = 0.012 ), and high treatment cost (P = 0.044 ). Duration of hospital stay was clearly correlated with the time spent at home prior to admission; spearmans rank correlation coefficient was 0.72 (95% CI 0.42–0.87). Conclusion. Delays in seeking treatment among BU patients were the main factor which resulted in most of the other factors contributing to the challenges in treatment. A combination of psychosocial and biomedical approach was proposed as holistic method to alleviate the challenges in BU treatment.