Effect of malnutrition on the pharmacokinetics of anti-TB drugs in Ghanaian children.

BACKGROUND: Anti-TB drugs dosing based on weight alone may contribute to suboptimal drug concentrations and poor treatment outcomes in malnourished children. We examined the effect of malnutrition on the pharmacokinetics (PK) of first-line anti-TB drugs in children.METHODS: Drug concentrations were measured in Ghanaian children during the intensive phase of TB treatment. Weight-for-age (WFA), height-for-age (HFA), weight-for-height (WFH) and body mass index-for-age (BFA) were calculated and children with Z-scores < -2 SD (standard deviations) were considered as having malnutrition. PK differences of anti-TB drugs were compared by nutritional status.RESULTS: Of 100 participants, 24/48 (50.0%) of those younger than 5 years had wasting, 58/86 (67.4%) were underweight, and 56/99 (56.6%) had stunting; 22/51 (43.1%) children aged ≥5 years had low BFA. Children with stunting were more likely than controls to have lower mean peak concentration (Cmax) and area under the curve (AUC0-8h) of rifampin (RIF) and pyrazinamide (PZA), as well as a higher frequency of Cmax below the normal range. Wasting and underweight were associated with lower mean ethambutol (EMB) Cmax and AUC0-8h.CONCLUSIONS: The current WHO-recommended dosages were associated with lower plasma exposure of RIF, PZA and EMB in children with stunting, wasting and underweight. Anti-TB drugs dosing models for children may need to include height.

Knowledge and Willingness to Donate Kidneys for Transplantation in Ghana: A Cross-Sectional Survey.

BACKGROUND: The main treatment modalities for chronic kidney disease (CKD) are dialysis and kidney transplantation. While kidney transplantation provides better survival and quality of life outcomes, it is a new treatment option in Ghana. Finding kidney donors for transplant may be a major challenge due to varied views of the public. METHODS: This cross-sectional study was carried out in 5 purposively selected communities in the Greater Accra region in Ghana. Structured questionnaires and standardized instruments were used to assess sociodemographic characteristics, spirituality, and perception of kidney transplantation. RESULTS: The mean age of the 480 participants was 29.60 ± 10.65 years. The proportion of men was 51%. The average score for knowledge of participants on kidney donation was 4.8 ± 2.6. The level of spirituality score was 25.4 ± 3.89. Approximately 48% (231/480) of participants were willing to donate a kidney while still alive. Willingness to donate when dead was 72% (344/480). Willingness to donate a kidney when dead was significantly lower among the participants in the older age groups. High level of knowledge about kidney transplantation, being employed, basic formal education, and never married were associated with willingness to donate kidney (P < .05). CONCLUSION: Our results suggest that participants have a low level of knowledge regarding kidney transplantation, while about two-thirds are willing to donate only after death. Continuous public education is key to raise public awareness of the need for kidney transplants. This will support the Ministry of Health in their efforts to institute a kidney transplant program in Ghana.

Plasma concentrations of transforming growth factor beta 1 in non-progressive HIV-1 infection correlates with markers of disease progression.

The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF ß 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n=14) and progressive infection (n=47), plasma levels of active TGF ß 1, INF-γ, TNF-α, IL-10, IL-1ß, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n=12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF ß 1 and IL-10 were significantly decreased while IL-1ß, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF ß 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1ß, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these findings may have implications for systemic cytokine-based therapies in HIV-1 infection.

Efficacy of Behavioural Graded Activity Compared with Conventional Exercise Therapy in Chronic Non-Specific Low Back Pain: Implication for Direct Health Care Cost.

BACKGROUND: The relative efficacy of conventional exercise therapy (CET) and behavioural graded activity (BGA) has not been fully established to inform the preference in clinical practice. OBJECTIVE: To compare CET and BGA on the treatment outcome of chronic non-specific low back pain (LBP). METHODOLOGY: Participants were assigned into either BGA or CET group in this randomized feasibility intervention. The CET group received supervised exercise therapy while BGA group engaged in individually prescribed sub-maximal activities based on time-contingent principles. Interventions were carried out twice weekly and over a period of 12 weeks. Outcome measures were numerical rating scale and RAND 36-item health survey which were administered at baseline, week 4 and week 12. Health care cost questionnaire was also administered to evaluate physiotherapy cost after 12 weeks. Mixed design two-way ANOVA with level of significance set as priori at p<0.05 was used to compare both groups. RESULTS: Seventy-seven and half percent (62) participants (CET=29 and BGA=33) with mean ages 45.0±12.2 and 43.1±13.2 years respectively, completed the study. Both groups improved significantly (p<0.001) during the intervention. However, there were no significant differences (p>0.05) between the treatment groups at any time points and for any measures assessed. Therapeutic benefits in both groups have bearing on direct health care costs. CONCLUSION: The results indicate that CET and BGA have similar outcomes in patients with chronic nonspecific LBP with regard to the pain and quality of life. Effective application may however be hampered by the cost-related factors thus suggesting evaluation of health care system in Ghana.

CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

Branched isomeric 1,2,3-triazolium-based ionic liquids: new insight into structure-property relationships.

A series of four isomeric 1,2,3-triazolium-based ionic liquids (ILs) with vary degree of branching were synthesized and characterized to investigate the effect of ion branching on thermal and physical properties of the resulting IL. It was found that increased branching led to a higher ionicity and higher viscosity. The thermal properties were also altered significantly and spectral changes in the near edge X-ray absorption fine structure (NEXAFS) spectra show that branching affects intermolecular interaction. While the ionicity and viscosity varying linearly with branching, the MDSC and NEXAFS measurements show that the cation shape has a stronger influence on the melting temperature and absorptive properties than the number of branched alkyl substituents.

Causes of Death in Hospitalized HIV Patients in the Early Anti-Retroviral Therapy Era.

OBJECTIVE: To establish the cause(s) of death among persons with HIV and AIDS admitted to the Fevers Unit of the Korle-Bu Teaching Hospital (KBTH) in 2007 and to determine whether they were AIDS-related in the era of availability of HAART. METHOD: Retrospective chart review of all deaths that occurred in the year 2007 among inpatients with HIV infection. Cause of Death (COD) was established with post mortem diagnosis, where not available ICD-10 was reviewed independently by two physicians experienced in HIV medicine and a consensus reached as to the most likely COD. RESULTS: In the year under review, 215 (97%) of the 221 adult deaths studied were caused by AIDS and HIV-associated illnesses. Of these, 123 (55.7%) were due to an AIDS-defining illness as described in CDC Category 3 or WHO stage 4. Infections accounted for most of the deaths 158 (71.5%), many of them opportunistic 82 (51.8%). Tuberculosis was the commonest COD. Clinical diagnosis of TB was accurate in 54% of deaths, but was not validated by autopsy in 36% of deaths. There were few deaths (14.5%) in patients on HAART. CONCLUSION: In a developing country like Ghana where HAART was still not fully accessible, AIDS-related events remained the major causes of death in persons living with HIV. Total scale-up of the ART programme with continuous availability of antiretrovirals is therefore imperative to reduce deaths from AIDS and HIV associated illnesses. There is need for interventions for early diagnosis as well as reduction in late presentation and also better diagnostic tools for tuberculosis.

Disseminated cryptococcosis in a patient with HIV/AIDS at a teaching hospital in Ghana.

OBJECTIVE: To raise awareness of the existence of cryptococcal infections in HIV/AIDS patients in Ghana. METHOD: Detailed postmortem gross and histopathological analysis of an HIV/AIDS patient suspected to have cryptococcal meningitis was carried out and histopathological findings correlated with clinical findings. RESULTS: showed disseminated Cryptococcosis in an HIV/AIDS patient which was confirmed with special stains. CONCLUSION: cryptococcal infection occurs in HIV /AIDS patients in Ghanaian and when clinically suspected the diagnosis should be pursued vigorously.

CUTANEOUS INVOLVEMENT OF HODGKIN LYMPHOMA IN A CHILD--CASE REPORT.

Specific cutaneous involvement in Hodgkin Lymphoma is rare and has not been reported in the younger paediatric age group. We report a case of a ten year old girl who presented with specific cutaneous involvement, confirmed using immunohistochemical stains. Treatment with combination chemotherapy resulted in rapid disappearance of the lesions and contrary to the generally poor prognosis associated with most other such reported cases in adults, she has clinically remained disease free two and a half years post treatment. Obtaining an accurate pathological diagnosis is essential to ensure appropriate treatment even in resource limited settings as illustrated by this case.

Causes of Death in Hospitalized HIV Patients in the Early Anti-Retroviral Therapy Era

Objective: To establish the cause(s) of death among persons with HIV and AIDS admitted to the Fevers Unit of the Korle-Bu Teaching Hospital (KBTH) in 2007 and to determine whether they were AIDS-relatedin the era of availability of HAART Method: Retrospective chart review of all deaths that occurred in the year 2007 among inpatients with HIV infection. Cause of Death (COD) was established with post mortem diagnosis; where not available ICD-10 was reviewed independently by two physicians experienced in HIV medicine and a consensus reached as to the most likely COD. Results: In the year under review; 215 (97) of the 221 adult deaths studied were caused by AIDS and HIV-associated illnesses. Of these; 123 (55.7) were due to an AIDS-defining illness as described in CDC Category 3 or WHO stage 4. Infections accounted for most of the deaths 158 (71.5); many of them opportunistic 82 (51.8). Tuberculosis was the commonest COD. Clinical diagnosis of TB was accurate in 54 of deaths; but was not validated by autopsy in 36 of deaths. There were few deaths (14.5) in patients on HAART. Conclusion: In a developing country like Ghana where HAART was still not fully accessible; AIDS-related events remained the major causes of death in persons living with HIV. Total scale-up of the ART programme with continuous availability of antiretrovirals is therefore imperative to reduce deaths from AIDS and HIV associated illnesses. There is need for interventions for early diagnosis as well as reduction in late presentation and also better diagnostic tools for tuberculosis

Treatment default among patients initiating HAART at the Korle-Bu Teaching Hospital in Accra, Ghana.

BACKGROUND: Loss-to-follow-up (LTFU) during highly active antiretroviral therapy (HAART) may lead to treatment failure and increased mortality among HIV-infected patients. We investigated LTFU rate among HIV-infected patients at Korle-Bu Teaching Hospital (KBTH), and sought to identify sub-groups at-risk for treatment default in order to improve outcomes among high-risk patients. STUDY DESIGN: We conducted a cross-sectional retrospective chart review of 290 HIV-infected patients who initiated HAART at KBTH between January 1, 2008, and June 31, 2008. Patients were classified as LTFU if they did not return for regularly scheduled care within the study period. Chi-square and t-tests were used to compare demographic and clinical characteristics of patients continuing treatment and those who defaulted. RESULTS: Of the 290 patients who initiated HAART, 41 (14%) defaulted, and 7 (2%) died during the 18-month study period. The mean age was 38.7 ± 9.4 years and 184 (64%) were female. The mean baseline CD4 cell count was 183 ± 144 cells/µl. Age, gender, educational level, marital status, presence of opportunistic infection, body mass index, baseline CD4 cell count, WHO disease stage 3 or 4, HAART initiation while pregnant, incidence of poor adherence, and time to initiating HAART after clinic enrollment were not associated with treatment default (P> 0.05). CONCLUSION: A majority of patients initiating HAART in an urban Ghanaian clinic remained in care through one-year of follow-up. Patients who defaulted therapy were indistinguishable demographically and clinically from those who remained in care. Standardized pre-treatment adherence counseling sessions may have influenced the favorable outcomes.

Highly active antiretroviral therapy and employment status in accra, ghana.

OBJECTIVES: This study investigated the immunologic responses and employment history of highly-active antiretroviral therapy (HAART) patients. DESIGN: We interviewed patients and reviewed medical records to collect demographic, clinical, and employment history while on HAART. Demographic characteristics were tested as predictors of immunological response while on HAART using hierarchical linear models. SETTING: Fevers Unit, Korle-Bu Teaching Hospital, Accra, Ghana PARTICIPANTS: Subjects comprised a convenience sample of adult HAART patients receiving therapy for at least 9 months. 270 patients were interviewed. 38 were excluded due to inadequate time on HAART or inability to locate all necessary patient information. INTERVENTION: This was an observational study. MAIN OUTCOME MEASURES: We investigated the change in CD4 cell count and weight since the initiation of therapy, and their ability to maintain or regain employment as well as the reasons for this. RESULTS: The estimated mean ± standard error increase in CD4 cell count from baseline at 6, 12, and 18 months were 102 ± 5, 204 ± 11, and 236 ± 10 cells/µL, respectively. Overall, 147 patients (63.4%) reported remaining employed or obtaining new employment while on HAART. Patients who were asymptomatic at initial presentation were more likely to remain employed or returned to work while on HAART than those who were symptomatic (66.4% vs. 48.8%, P = 0.009). Most patients were employed in the informal sector, which made their economic situation particularly vulnerable to HIV-associated illness. CONCLUSION: The findings suggest that patients receiving HAART experience good clinical and immunological responses as well as improvement in employment status.

Initiating antiretroviral treatment in a resource-constrained setting: does clinical staging effectively identify patients in need?

In industrialized countries, the initiation of antiretroviral therapy (ART) is based on virological, immunological and clinical markers. The objective of this study was to identify treatment gaps when ART initiation is based on clinical staging alone. The method employed was a retrospective study of 5784 patients enrolled in an HIV treatment programme in two urban and two rural sites in Ghana. Of the patients, 29.5% were in clinical Stages I and II and had a CD4+ T-lymphocyte count less than 200 cells/mm(3). Significantly more patients in clinical Stage I from urban sites (37.0%) had a CD4+ T-lymphocyte count less than 200 cells/mm(3) as compared with patients from rural sites (23.8%) (P value <0.05). In addition, more men (39.9%) in clinical Stage I had a CD4+ T-lymphocyte count less than 200 cells/mm(3) when compared with women (27.4%) (P value <0.05). In conclusion, clinical staging cannot identify a relatively large number of patients who need ART. A wider availability of CD4+ T-lymphocyte count testing will optimize the identification of patients eligible for ART.

Diagnosis of dual human immunodeficiency virus types 1 and 2 infections in a resource-limited setting.

BACKGROUND: The presence of dual HIV-1/HIV-2 infection in Ghana and the different drug requirements for the treatment of HIV-1 and HIV-2 presents difficulties for the treatment of dual infections with both viruses. OBJECTIVES: To determine the prevalence of the dual sero-positive profile in treatment naive patients at a principal ART Clinic in Accra, Ghana and to investigate if rapid screening assays could be useful for diagnosis. DESIGN: A cross-sectional study. SETTING: A principal antiretroviral treatment centre in Accra, Ghana. SUBJECTS: Three hundred and twenty eight antiretroviral treatment naive patients. RESULTS: A total of 12 (3.7%) of patients seen were dual seropositive. There was a slight tendency of dual seropositive females being older than their HIV-1 counterparts (p = 0.088, CI = -10.833 to 0.753). Eight of the 12 of the dual seropositives were reactive for Genie II and were considered as possibly infected with both HIV-I and HIV-2. Seven (87.5%) of Genie II dual seropositives had strong intensities (> 1+) on both HIV-2 specific bands (sgp105 and gp36) on Innolia. CD4 counts were not significantly different in dual seropositives as compared to HIV-1 infected patients. CONCLUSIONS: Dual HIV-1/HIV-2 seropositives (and possibly infections) maybe common especially in older women. The Genie II will be useful as a supplemental rapid test for rapid and accurate differentiation of HIV-1 and HIV-2 antibodies at treatment centres.

Adult tetanus in Accra, why the high mortality? An audit of clinical management of tetanus.

BACKGROUND: Tetanus is a life threatening infection relatively uncommon in the developed countries but occurs frequently in developing countries with case fatality rates of 40-60 %. Recent review of adult tetanus at the Korle-bu Teaching Hospital showed a high case fatality of 50%. In order to determine the factors underlying this high case fatality we conducted a retrospective clinical audit of the clinical management of adult tetanus admitted in 1994 to 2001 to the Korle-bu Teaching Hospital. METHODS: Data extracted from the admission and discharge books of the Fevers' Unit of Korle-bu Teaching Hospital, Accra and patient case notes were examined and analysed. RESULTS: Case fatality rate (CFR) varied from 25 % in 1999 to 72.7% in 2001. There was no gender difference in the case fatality. There was no significant difference in the mean age of those who died and those who survived, however, the CFR rose with age. The presence of neck and a dirty wound were associated with increased CFR. The CFR correlated with the severity of tetanus and increased when an expected treatment action, wound debridement, administration of antibiotics and/or immunoglobulin, was not performed. The administration of anti-tetanus toxin was associated with an increased CFR. CONCLUSION: The high case fatality rate in Accra was due to inappropriate management with most of the patients not treated with immunoglobulin and antibiotics and had inadequate wound care.

Cryptosporidium oocysts in Ghanaian AIDS patients with diarrhoea.

BACKGROUND: Although Cryptosporidiumspp. infections in acquired immunodeficiency syndrome patients (AIDS) with chronic diarrhoea have been reported in several African countries, there is no information regarding cryptosporidial diarrhoea in Ghanaian AIDS patients. OBJECTIVE: To investigate the occurrence of C. parvum and other gastrointestinal parasitic agents in Ghanaian AIDS patients with chronic diarrhoea. DESIGN: Prospective study of HIV/AIDS patients with diarrhoea over a nine month period. SETTING: Korle-Bu Teaching Hospital and Korle-Bu Polyclinic Accra, Ghana. RESULTS: Analysis of stool specimens from clinically diagnosed HIV/AIDS (n = 21; mean CD4 count was 288 cells per microliter, 95% confidence interval of 237 to 340 cells per microliter) and HIV-seronegative (n = 27) patients revealed C. parvum in six (28.6%) of HIV/AIDS and 10 (37.0%) of the HIV-seronegative patients, respectively. Three other HIV/AIDS cases had other infections involving Strongyloides stercoralis 4.8% (1/21) and Salmonella spp. 9.5% (2/21). There was no concomitant association between C. parvum and any other parasites found. Also, no enterobacteria was found in the HIV-seronegative patients. CONCLUSION: This study demonstrates the prevalence of Cryptosporidium sp. in both HIV/ AIDS and HIV-seronegative individuals in Ghana. However, there was no statistical association between cryptosporidiosis and HIV/AIDS (p > 0.05).