Animal research highlights a therapeutic potential of cannabinoids for the treatment of depression Regina A. Mangieri Department of Pharmacology, The University of Texas at Austin, Austin, TX 78712, USA Abstract Long known for their mood altering effects, cannabinoids are currently under investigation for their therapeutic potential in the treatment of depression. Findings from multi
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Microsoft word - new_ijmms-10-039__autosaved_.docxRIF 1(5):218-223 (2010) ISSN:1837-6746
Evaluation of the efficacy of directly observed treatment short course (DOTS) in patients with
tuberculosis and HIV Co-infection in Kano, Nigeria.
Mukhtar M. Dauda (Ph.D)
Department of Biological Sciences, Microbiology Programme, Bayero University, Kano, Nigeria
Corresponding author: firstname.lastname@example.org
Background: A prospective study to assess the outcome of the directly observed treatment short course (DOTS) in tuberculosis patients
with HIV co – infection was conducted in Kano, Nigeria between 2005 and 2006.
Methods: The study group included one thousand six hundred and ninety two Tuberculosis patients (1066 men and 626 women) aged
15years and above. The recruitment protocol involved patients clinically diagnosed by X – ray and Mantoux test but with no previous
tuberculosis treatment whose initial sputum demonstrated acid fast bacilli (AFB) on at least two occasions as confirmed by Ziehl Neelsen
techniques and microscopical procedures. HIV serostatus was confirmed using HIV-1/HIV-2 ELISA Capillus, Geni-II HIV1/HIV2 kit
and Determine HIV1/2 protocols. Standardized treatment regimen containing isoniazid, rifampicin, pyrazinamide and ethambutol were
administered to the in patients for two months as intensive phase under the researchers direct clinical observation and monitoring.
Treatment and follow up continued to the eighth month while the outcome of cure, were assessed using standard protocols.
Results:A total of six hundred and fifty (38.4%) sputum smear acid fast bacilli (AFB) positive patients(391 male and 259 female) were
found to be sero positive for HIV. Treatment success rates after completion of dose regimen was 40% (261), of which 91% were sputum
negative for AFB after the first treatment phase of two months. This increased to 94% and 97% by the 5th and 8th month respectively.
Conclusion: An incidence of 38.4% of HIV/TB co-infection was reported at the Kano State Government officially designated Infectious
Disease Hospital (IDH) Kano (2005 – 2006). However, chemotherapy by DOTS was able to cure only 40% of patients, indicating
efficacy much lower than the 85% targeted by the World Health Organization(WHO). Thus, new regimens and administration protocols
Keywords: Tuberculosis / HIV Co – infection, chemotherapy DOTS, Nigeria
Tuberculosis is an air borne infection caused by the tubercle
tuberculosis occur each year with an estimated 2% annual risk bacillus Mycobacterium tuberculosis . It is a global health of infection in Nigeria . A study in Calabar, Cross River priority being a killer disease that manifests in its pulmonary State, Nigeria also recently showed no decline in the intensity form in up to 70% of cases or as extra pulmonary affecting all of the disease inspite of DOTS . Globally sub – Saharan parts of the body . An estimated seven million new cases Africa has the highest rate of tuberculosis as well as HIV/AIDS occur each year, resulting in 2 – 3 million deaths despite being . Today almost 70% of those co – infected with tuberculosis curable and preventable with effective treatment regimens and and HIV/AIDS live in Africa. The high rates of Human vaccines . Improvement in case identification and Immunodeficiency Virus/Acquired Immunodeficiency Synd- compliance with appropriate treatment remains a major rome (HIV/AIDS) have caused a sharp rise in the prevalence of challenge . Nigeria as the most populous country in sub- tuberculosis . For example in Kenya, the number of new TB Saharan Africa, carries the highest burden of tuberculosis and cases is increasing at the alarming rate of 12% each year. In has placed it among the top five of the WHO 22 high burden Nigeria, Ethiopia, and South Africa the rate is increasing at 7% tuberculosis countries . Available data reported that about annually. This was in contrast to a global annual rate of 200,000 of all types and 100,000 of new sputum positive increase of TB of just 0.4%. HIV/AIDS is the single most important factor fuelling the increasing incidence of TB over limited country like Nigeria where TB is a leading cause of the last decade [5, 6]. The profound immune suppression of death. This is of particular importance to Global HIV control HIV infection on active TB, has also increased the rate of programme. It is in line with these needs that the present study recurrence of tuberculosis [7, 8]. Another study in Nigeria was conducted for the first time in Kano, an area in Northern showed a median HIV prevalence of 17.0% (range 4.2% - Nigeria with particular emphasis on evaluating the efficacy of 35.1%) among the TB patients. The highest prevalence was DOTS regimen and the outcome of sputum smear positive recorded in the north central state of Benue and the least was at pulmonary tuberculosis patients with the HIV co – infection the South-West state of Oyo . Kano state recorded 12.4% in attending the Infectious Diseases Hospital in Kano Nigeria that survey .This ranks the state as one of the vulnerable TB /HIV regions in Africa . In a study in Maiduguri Nigeria, a 69.4% mycobacterium infection among HIV–seropositive Material and methods
patients was reported . A similar study in Jos, Nigeria reported a 12.6% rate of HIV/TB co-infection . The global Study Area
increase in the problem is not a lack of an effective treatment but that of properly applied short course chemotherapy. The The study area was Kano state in northern Nigeria. It is located WHO and the International Union Against Tuberculosis and within savanna, latitude 120 to 120 15’ N and longitude 80 301 to Lung Disease (IUATLD) have recommended Directly 451 E. It has an elevation of about 525 meters above the sea Observed treatment short course (DOTS) strategy for the level with a population of 12.4 million. control of tuberculosis [5,10]. The essential features of DOTS strategy include government commitment to the TB control The Hospital for the study
program, a secured supply of drugs, diagnosis based on sputum smear examination by microscopy in symptomatic patients, a The study was carried out between January 2005 and August, reporting system and supervision of short course therapy using 2006 at the Infectious Diseases Hospital (IDH), Kano. It was isoniazid, pyrazinamide and ethambutol including rifampicin in the main Kano State Government official hospital designated to at least the intensive phase of treatment . Treatment success treat and manage infectious diseases. The hospital receives in DOTS remains much higher than in non DOTS areas . patients from the whole of Northern Nigeria, and serves as The DOTS strategy can be successfully implemented in even referral center for tuberculosis and HIV/AIDS control activities difficult conditions as those found in Cambodia . Each not only for Kano and other neighboring states but also for country is to identify based on the local information, the Niger and Cameroon republics. All Tuberculosis and combination of drugs to be used for the DOTS. Nigerian HIV/AIDS related medical care are provided free of charge to National Tuberculosis and Leprosy Control Programme in line the patients at the hospital, which has a chest clinic, that runs with the World Health Organization (WHO) and the everyday and receives an average of 200 patients a day. There International Union Against Tuberculosis and Lung Disease are wards for in-patients admission, laboratory services, HIV (IUATLD) recommendation have defined for new cases counseling and testing center, and TB and HIV collaborative treatment (Category 1); that is, two months of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol as intensive phase, and 6 months continuation phase using Isoniazid and Subjects for the Study
Ethambutol. These drugs can be used as loose or in fixed drugs combination . For adequate tuberculosis treatment, an The subjects were both male and female patients that presented appropriate combination of anti – tuberculosis drugs taken to the Chest Clinic with symptoms of pulmonary Tuberculosis regularly by the patients under direct observation for the based on the history and clinical examination and whose initial prescribed period of time is required . Studies on treatment sputum smears demonstrated acid fast bacilli (AFB) by direct outcome of human pulmonary TB patients with or without HIV smear sputum on microscopy using Ziehl – Nelseen stain at Co – infection have been reported from elsewhere in Nigeria least on at least two occasions in line with the recommendations . For example a study conducted in Sagamu, South western of WHO [19,20]. The subjects are confirmed as TB patients Nigeria, showed a cure rate of 76.8% although still lower than through standard clinical and diagnostic investigations which the World Health Organization recommended target of 85% . The trend of pulmonary TB in-patients seen at six DOTS clinics in the Federal Capital Territory, Abuja Nigeria Clinical and Diagnostic Features for TB Investigation
demonstrated a high prevalence of infectious TB in the population screened . The authors alleged development of Routine Chest X – ray was carried out on the suspected patients resistance to current anti – TB drugs. However, such cohort who presented with chronic deep seated productive cough with studies in Kano northern Nigeria are yet to be reported. It is or without haemoptysis and Bronchopneumonia. This was relevant to evaluate the efficacy of DOTS regimen for followed by Tuberculosis testing with 10 units of tuberculin tuberculosis in patients with HIV co-infection in a resource administered subdermally by Mantoux technique . TB was suspected when a positive Mantoux showed ≥5mm induration. and the other positive) the HIV status was recorded as Chest X – ray film was carried out to evaluate for primary indeterminate. The indeterminate result was then resolved by a tuberculosis. Evidence of hilar gland enlargement, thousands of tie – breaker which is Determine. This confirms the final result small nodules, millet size all of similar size and distributed as positive or negative for HIV [15, 16]. All the patients that through out the lungs confirmed Miliary TB. The presence of refused HIV testing after counseling and those with lung cavitations as mark of post primary TB  was also indeterminate results were excluded from the study. assessed. The method confirmed presence of Acid fast bacilli (AFB) in the sputum that was expectorated from a deep cough Specimen Collection and Microscopy
The patients submitted three sputum specimens over two Subject Selection Criteria
consecutive days. The first smears were prepared, fixed and stained by Ziehl – Neelsen staining methods for acid fast bacilli The subjects for the study were selected based on certain (AFB). The smears were examined for acid fast bacilli under oil criteria, this is because of the need to have patients who can be immersion (x 100) objective [19, 20, 21]. relied upon to complete full duration of the treatment and the finding of the study will be applicable to a large population. Treatment and Follow-up of Patient
Eligibility and exclusion criteria are presented in the following A category I standard regimen of never previously treated cases comprising of ethambutol, isoniazid, rifampicin and pyrazinamide was used for the treatment of smear positive Eligibility Criteria
cases as recommended by the International Union against Tuberculosis and Lung Diseases (IULTD) and World Health Organization  and as demonstrated in Sagamu southern - 15 years old
Intensive phase of treatment
All subjects were admitted to the test ward of the hospital for - Available for follow – up for the period of study two months. Treatment was administered by DOTS regimen. The patients swallowed the tablets under the supervision of a Exclusion Criteria
health worker. Fixed drugs combination tablet of Pyrazinamide, Rifampicin, Ethambutol and Isoniazid, were used. Subjects were discharged after the two months intensive phase. The initial phase of treatment was prolonged by one month in case of smear positivity. At the end of the prolongation, another sputum smear was examined and the continuation phase started irrespective of the latter result. Continuation phase and their duration remained unchanged despite prolongation of the initial HIV Counseling and Testing procedure
Each patient’s informed consent to participate in the study was Continuation phase of treatment
sought for and was offered confidential HIV testing accompanied by pre and post test counseling according to This entailed a monthly collection by the patients at the DOTS National AIDS Programs guidelines. Those that agreed to be clinic for six months. Self administered fixed drugs tested had blood sample taken for HIV test. The investigation combination of Ethambutol and Isoniazid were used. The return was performed according to the standard hospital practice and of empty blister of packs of drugs signaled completion of followed guidelines developed by the National HIV Rapid Test Algorithm. The ELISA Test of Capillus HIV-1/HIV-2 (Trinity, Biotech, Ireland); Genie II (HIV-1/HIV-2 test kit Bio-Rad Monitoring of Patient
Laboratories France) and Determine HIV1/2 (Inverness medical, UK) were followed [14,15]. HIV serostatus was The sputum, of all the patients were re-examined at second, recorded as positive if Capillus and Genie II tests were positive. fifth and seventh months and two smears were taken one over Otherwise the result was negative if both Capillus and Genie II were negative. When the two tests showed discordant result (that is Capillus and Genie II did not agree, one being negative Treatment Outcome
Statistical analysis of the Data
Treatment outcomes as recommended by WHO and the IUATLD, and adapted in Nigeria [17, 21, 22] were categorized Treatment outcomes between different groups were compared as cured, treatment completed, treatment failure, died, defaulted using Chi – square (X2) test with difference at the 5% or transferred out. A patient was considered as “Cured” if a probability being regarded as significant. Descriptive statistics negative sputum smear (without AFB) was obtained in the last (numbers, percentage and means) were used in the analysis of month of treatment and at least one previous occasion. A patient was considered as having “Completed treatment” if treatment had been completed and smear examination results were available at the end of the treatment. “Treatment failure” was marked by becoming AFB sputum positive again at least Enrolments
five months after the commencement of treatment. A “Defaultor” was a patient who did not return to collect the anti- For the two year period of study, a total of 1,844 patients with tuberculosis for 8 weeks or more after the date of the last sputum smear positive tuberculosis were enrolled. Of these, 42 attendance during the course of treatment. A “Transferred out” patients were not counseled for HIV testing during the two was defined as a patient who was transferred to another months period of admission, 79 refused HIV testing after reporting unit and for whom the treatment result was unknown counseling, 19 refused admission in the ward, and in 12  Death was reported for patients who died during treatment, patients, the result were indeterminate. All these 152 patients
Table 1. The distribution of HIV/TB coinfected patients on DOTS by age and gender at Infectious Disease Hospital, Kano Nigeria in
2005 – 2006.
Table 2. Sputum conversion rate of seropositive TB patients at Pretreatment 2, 5 and 7months after treatment with standard
Number (%) positive for TB
Table 3. DOTS Treatment Outcome of TB/HIV seropsitive Patients in Kano Nigeria (2005-2006)
sputum conversion at the end of 2 months was similar for HIV positive and negative patients . The high sputum conversion Demographic Data
rate for HIV positive patients is an indication that the DOTS has the capacity for achieving good results even in settings with The study identified a total of 650 TB patients that were HIV- high HIV prevalence. Sputum conversion at 2 months is seropositive (Table 1). This HIV seropositive – TB cohorts was associated with good treatment outcomes. The study confirms made up of 40% females and 60% males. Although not that the possibility of reaching a cure which is higher among statistically significant (gender versus HIV positivity; X2=3.67; patients whose sputum has converted to AFB smear negative P=0.055), there was a higher proportion of HIV/TB co-infected than among those whose sputum remains positive after the first females (259), in comparison with males (391). two months of treatment which resulted in over 90% of patient showing no AFB. In Madagascar, the majority of failures were Sputum Conversion Rate
observed in patients who were smear positive at 2 months [22,23] Sputum conversion during the third month of treatment Sputum conversion after two months intensive phase was 91% is an important predictor of treatment success . This is in and as treatment continued to the seventh month only 3% of spite of the fact that some studies have demonstrated that HIV patients remained as TB (AFB) positive (Table 2). seropositive status is not a principal factor in delaying sputum conversion among patients receiving intensive phase Treatment outcome
tuberculosis treatment . The sputum conversion rate at the fifth month was 94.0% and rose to 97% by the seventh month The treatment outcome at the end of 8 months revealed that of therapy. However,19 patients (3%)had delayed sputum 40%(261) became cured. Ttreatment was completed by 26% conversion as noted at seventh through the eighth month. In (172). Ttreatment failure was recorded in 6% (39). A default of conclusion, we found, an incidence of 38.4% of HIV co- in 9%(57) was observed, while transfer out was 3% (18) and fection among people with AFB positive smears attending the 16%(103) deaths were recorded (Table 3). Infectious Diseases Hospital Kano, Nigeria (2005 – 2006). The study also showed a less than 50% cure rate which indicates a Discussion
low efficacy of DOTS. Although there was a high (91%) sputum conversion rate in the intensive phase, only 40% cure The treatment of tuberculosis especially when complicated by rate was achieved after 8 months of therapy. This is lower than HIV seems to be difficult even with DOTS therapy [4,5,17,18]. the WHO target of at least 85%, suggesting either an inadequate The success rate of 40% obtained from this study is less than duration of treatment or loss of efficacy, perhaps due to drug the global targets of 85% [17,23]. However, this can be resistance. A further need to improve the existing regimen with a better combination that could be more promising and cost considered to be impressive in view of the much lower success rates recorded before the introduction of the DOTS Authors’contribtions
programmes. Slightly greater success was reported in one study in Ilorin, Nigeria, that observed a 43.7% cure rate . Ymuhammad (MD) conceived of and conducted the study Another Study in Sagamu reported a 76.8% success . under the supervision of TI Oyeyi (PhD, Assoc.Professor) as However, in Calabar south- eastern Nigeria 42% cure rate was part of his research work for a PhD degree from Bayero found . The lower success rate of 40% recorded in this study University, Kano, Nigeria. MD Mukhtar (PhD, Assoc. resulted into a significantly high death rate of 16% among HIV Professor) internally supervised the work up to completion and positive patients. Progress in implementing effective drafted the manuscript. All authors read and contributed to the tuberculosis control based on the DOTS strategy has been slow; by 1999, only 40% of estimated treated new cases were reported to WHO (23% in DOTS programmes and 17% in non References
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British Journal of Psychotherapy Integration Vol 5-II, 2008 The wel tempered therapist Psychotherapy integration and the personality of the therapist "Every explicit duality is an implicit unity." Integration is inherent to the art and science of psychotherapy and constitutes a core function of the psychotherapeutic process. But integrative processes not only facilitate our cli