ADVERSE EVENTS TO FIRST LINE ANTI-TUBERCULOSIS DRUGS IN PATIENTS CO-INFECTED WITH HIV AND TUBERCULOSIS.

BACKGROUND: The combination and use of multiple drugs in the treatment of tuberculosis (TB) predispose to adverse drug events and reactions. This study evaluated the incidence, frequency, and severity of adverse events to first line anti-tuberculosis (anti-TB) drugs in patients with TB and co-infections with Human Immunodeficiency Virus (HIV). OBJECTIVE: The objective of this study was to determine the effects of HIV status on the risk of developing adverse events to first line anti-TB therapy. METHOD: The study was carried out between 2006 and 2007 when TB therapy was administered without concomitant anti-retroviral therapy. Patients with TB presenting at the chest clinic of a tertiary hospital were sequentially enrolled. Those with TB alone were allocated to the first group while those with TB-HIV infection were allocated to a second group. A checklist of adverse events to the drugs was used to screen for adverse drug events and reactions during the period of anti-TB therapy. Adverse drug events were graded as serious and others (mild-moderate). RESULTS: One hundred and three patients completed the study. Thirty one (30.1%) of the patients had TB-HIV co-infection. Majority (70.4%) of the events were detected during the first week of therapy, 92% of these events were mild-moderate. Eight (25.5%) of those with TB-HIV co-infection had serious adverse events. All the serious events occurred in the TB-HIV group. Independent factors for occurrence of ADEs include HIV status, increasing age, and female gender. CONCLUSION: The rate of adverse drug events among patients on first line antituberculosis treatment was higher in HIV co-infected patients.

ATTITUDE AND PRACTICE OF DOCTORS TOWARD ADVERSE DRUG REACTIONS (ADRs) REPORTING IN A NIGERIAN TERTIARY HEALTH FACILITY.

BACKGROUND: Adverse drug reactions, (ADRs), constitute an important cause of morbidity and mortality worldwide. Spontaneous adverse drug reaction (ADR) reporting is the bedrock of post-marketing surveillance but under-reporting remains its major drawback. OBJECTIVES: This study aimed at evaluating the attitude and practice of ADR among doctors in a tertiary health facility in Oyo State, Nigeria, with a view to improving ADRs reporting. METHODS: This was a cross-sectional questionnaire based study involving medical doctors working at the Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Ogbomoso. Consenting doctors were evaluated on their attitude and practice of ADRs through self-administered questionnaire. Data obtained were entered and analyzed using SPSS version 17. RESULTS: A total of 35 doctors responded to the questionnaires. Only about 57.1% considered ADR before prescribing, all of whom were also aware of the procedure for reporting. Awareness of the existence of National Pharmacovigilance Center (NPC) was 71.4%. Thirty (85.7%) of the respondents have encountered ADR, but only 2.9% have ever reported it with yellow form. Majority (85.7%) of the respondents did not consider ADR reporting as a useful tool in the prevention of drug related morbidities and mortalities. Other factors that may hinder ADR reporting include: lack of awareness of the existence of yellow forms for reporting (68.6%) and poor knowledge of procedure for reporting (48.6%). CONCLUSION: ADR reporting rate was very low among the participants in this small study; large studies aimed at evaluating the determinants of ADR reporting should be considered. Should these findings be confirmed, training and re-retraining through Continuing Medical Education (CME), and establishment of pharmacovigilance committee would be required to ensure a national pharmaovigilance system.

Attitude and practice of doctors toward adverse drug reactions (adrs) reporting in a Nigerian tertiary health facility

Background : Adverse drug reactions; (ADRs); constitute an important cause of morbidity and mortality worldwide. Spontaneous adverse drug reaction (ADR) reporting is the bedrock of post-marketing surveillance but under-reporting remains its major drawback. Objectives : This study aimed at evaluating the attitude and practice of ADR among doctors in a tertiary health facility in Oyo State; Nigeria; with a view to improving ADRs reporting. Methods : This was a cross-sectional questionnaire based study involving medical doctors working at the Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital; Ogbomoso. Consenting doctors were evaluated on their attitude and practice of ADRs through self-administered questionnaire. Data obtained were entered and analyzed using SPSS version 17. Results : A total of 35 doctors responded to the questionnaires. Only about 57.1 considered ADR before prescribing; all of whom were also aware of the procedure for reporting. Awareness of the existence of National Pharmacovigilance Center (NPC) was 71.4. Thirty (85.7) of the respondents have encountered ADR; but only 2.9 have ever reported it with yellow form. Majority (85.7) of the respondents did not consider ADR reporting as a useful tool in the prevention of drug related morbidities and mortalities. Other factors that may hinder ADR reporting include: lack of awareness of the existence of yellow forms for reporting (68.6) and poor knowledge of procedure for reporting (48.6). Conclusion : ADR reporting rate was very low among the participants in this small study; large studies aimed at evaluating the determinants of ADR reporting should be considered. Should these findings be confirmed; training and re-retraining through Continuing Medical Education (CME); and establishment of pharmacovigilance committee would be required to ensure a national pharmaovigilance system

Use and effectiveness of commercial flit-spray insecticides in control of mosquito population in Sagamu, Southwest Nigeria.

INTRODUCTION: Control of mosquito vector is crucial to reducing the burden of malaria in endemic region. In the present study, we investigated the use of commercial insecticides in families and their effectiveness in control of mosquito population in Sagamu, southwest Nigeria. MATERIALS AND METHODS: A pretested structured questionnaire was used to determine mosquito adulticides techniques employed in the community and most commonly used adulticides were evaluated for effectiveness by exposing adult mosquitoes to varying concentrations of the insecticides and responses monitored. RESULTS: Families differ in methods adopted to prevent mosquito and use of flit-spray insecticide was commoner. Although parents constitute 64% of those applying the insecticide, 22.2% were children. Household pyrethroid insecticide products of Baygon (Imiprothrin, Prallethrin plus Cyfluthrin), Mobil (Neopynamin, Prallethrin plus Cyphenothrin) and Raid (Pynamin forte, Neopynamin plus Deltimethrin) were three commonly used in the community. The exposure tie interval for eath of osquitoes was shorter with Raid (100% at 8 minutes) when compared with Mobil (80%) and Baygon (85%) at 10 minutes (p = 0.005). Kaplan-Meier survival curve of cumulative probability of surviving exposure to insecticide was lowest with Raid (log rank 2 = 14.56, P = 0.001). CONCLUSION: Although flit-spray insecticides are affordable with simple application tool, inexplicit use-instruction on labels may cause discrepancies in application. Monitoring responses of mosquitoes to commercial flit-spray insecticide may support effective control technique and prevention of vector resistance in poor resource communities.

Intermittent preventive treatment during pregnancy with sulphadoxine-pyrimethamine may promote Plasmodium falciparum gametocytogenesis.

OBJECTIVES: To determine the incidence of gametocytes and the propensity of sulphadoxine-pyrimethamine to promote gametocytogenesis when used as intermittent preventive treatment in pregnancy. SUBJECTS AND METHODS: This observational non-interventional study assessed the influence of intermittent preventive treatment with sulphadoxine-pyrimethamine on Plasmodium falciparum gametocytaemia among Nigerian pregnant women. A total of 306 pregnant women were enrolled in the study. RESULTS: The 306 pregnant women had 711 events, of which 31 pure gametocytaemic episodes were documented and 27 were recorded among the intermittent preventive treatment users. Only 4 episodes of pure gametocytaemia were recorded in pregnant women who did not receive any dose of sulphadoxine-pyrimethamine (27/129 vs. 4/276, χ(2) = 15.9, p = 0.00006). CONCLUSION: Our findings show that intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine may predispose to gametocyte carriage in pregnant women resident in the hyperendemic malaria region of southwest Nigeria. We therefore suggest that the use of insecticide-treated nets be encouraged among pregnant women resident in malaria-endemic sub-Saharan Africa in order to reduce malaria transmission.

The role of plasma melatonin and vitamins C and B12 in the development of idiopathic tinnitus in the elderly.

BACKGROUND: To determine the correlation between plasma levels of melatonin, vitamin C and vitamin B12 and the presence of tinnitus among elderly subjects with unexplained subjective tinnitus. METHOD: Prospective involving apparently healthy elderly with subjective tinnitus and those without. Plasma levels of melatonin, vitamin C and vitamin B12 were determined using high performance liquid chromatography and correlation determined by comparing subjects with and without tinnitus. RESULT: There were 139 elderly subjects (78 females and 61males), the mean(SD) range of the age was 66.9years (0.77) 60-98 years. Of these 58.3% had tinnitus. The mean (SD) range of the plasma levels of melatoninn was 11.2 pg/mL(4.2) 5.1 pg/mL - 30.2 pg/mL while that of Vitamin C was 0.7 µmol/L (0.1) 0.3 µmol/L - 1.2 µmol/L, and vitamin B12 was 43.0pmol/L (3.1) 25.4 pmol/L - 71.6pmol/L. Comparing the plasma levels of the markers between elderly with and those without tinnitus, the plasma levels of melatonin (p=0.01) and vitamin B12 (p=0.03) were significantly lower among the elderly with tinnitus compared to those without, while the difference in the plasma level of vitamin C (p=0.6) was not. CONCLUSION: Low plasma melatonin and vitamin B12 have significant correlation with the development of subjective idiopathic tinnitus among the elderly. This finding suggests the need for the trial of correction of these markers in the reversal or control of tinnitus.

Predictors of asymptomatic malaria in pregnancy.

A number of studies have described malaria parasitaemia in pregnancy as mostly an asymptomatic condition, however information about predictors of asymptomatic malaria is largely lacking. We investigated the prevalence of symptoms and potential predictors of asymptomatic malaria in pregnant women attending Ante-Natal Clinic (ANC) of two public maternity hospitals in Ibadan, Southwest-Nigeria. Demographic data, history of previous and present pregnancy were obtained from the subjects and blood smears were examined for malaria diagnosis by light microscopy. Seventy - seven parasitaemic pregnant women attending antenatal clinic were evaluated for presence or absence of symptoms that may be associated with malaria. Thirty-seven women (48%) were asymptomatic whereas 40 (52%) presented with symptoms such as weakness, headache and general body ache and fever. Parasite density was significantly higher in symptomatic patients (P = 0.042), while asymptomatic patients had low level parasitaemia but significantly higher gametocyte carriage (P = 0.035). In conclusion, parasitaemic pregnant women resident in hyper- or holo-endemic malaria region are likely to be symptomatic with increasing density of the parasitaemia.

Comparative study of efficacy of artesunate plus cotrimoxazole and artesunate plus chloroquine in the treatment of malaria in Nigerian children: a preliminary report.

BACKGROUND & OBJECTIVES: The study was undertaken to evaluate the efficacy of cotrimoxazole plus artesunate and to compare the efficacy of this combination with that of artesunate plus chloroquine in the treatment of acute uncomplicated falciparum malaria in children. METHODS: Children aged between 0.5 and 12 yr with clinical and parasitological evidence of Plasmodium falciparum malaria were randomized to receive either artesunate plus cotrimoxazole or artesunate plus chloroquine. They were followed-up with clinical and parasitological assessment for a period of 14 days. RESULTS: In all, 57 out of 81 (31 in the artesunate plus cotrimoxazole group and 26 in artesunate plus chloroquine group) completed the study as per protocol and were evaluated. Pre-treatment clinical and parasitological parameters were similar in the two treatment groups. The time to clear fever and other symptoms were similar in the two groups 1.0 +/- 0 vs 1.14 +/- 0.38 (p > 0.05). Parasite clearance times were also similar; 1.65 +/- 0.49 days vs 1.58 +/- 0.67 days respectively for artesunate plus cotrimoxazole and artesunate plus chloroquine (p > 0.05). The cure rates on Day 14 were 100% for both artesunate plus cotrimoxazole and artesunate plus chloroquine groups. Both drug combinations were well-tolerated in the small population of children. CONCLUSION: These results indicate that artesunate plus cotrimoxazole has similar efficacy to artesunate plus chloroquine in the treatment of acute uncomplicated P. falciparum malaria in children resident in an endemic area of south-west Nigeria.

Malaria: passive case detection and healthcare providers' choices of chemotherapy.

Prompt diagnosis and treatment play a central role in the malaria control programme in sub Saharan Africa. However, in most cases the diagnoses are never confirmed either for lack of facility or disinterest of healthcare providers resulting in over-diagnosis. To determine the proportion of clinically diagnosed malaria cases who could be confirmed with microscopy and evaluate compliance of healthcare providers with the National treatment guidelines for malaria. Participants were patients referred for malaria microscopy after the attending physicians had made clinical diagnosis of malaria. Thick blood smears were made under strict asepsis, stained and thereafter examined under oil immersion objective lens. Of the 630 patients who were referred with clinical impression of malaria, only 224 or 35.6% were positive for malaria parasite. The slide positive patients were younger with a mean age of 10.6 +/- 13.0 years versus 17.2 +/- 18.5 years [P < 0.005] for the slide negative individuals. There were only few instances of non-compliance with the National treatment guidelines for malaria. In conclusion, there appears to be over-diagnosis of malaria considering that only about a third of the clinical malaria cases were confirmed by microscopy. There is need for large epidemiological studies and possible policy review.

Cotrimoxazole, clinical uses and malaria chemotherapy.

Microbial infections still account for considerable morbidity and mortality in sub-Saharan Africa. The importance of chemotherapeutic agents cannot be over-emphasized. Some antimicrobial agents provide broad spectrum of activity spanning different classes of bacterial and protozoan diseases. Cotrimoxazole, an antifolate antimicrobial was originally meant for treatment of bacterial diseases but has been shown to be an effective drug in the treatment of malaria amongst other conditions. This review attempted to explore the pharmacology of cotrimoxazole, its many clinical uses and adverse effects. Specific experiences of the author in the application of cotrimoxazole in the treatment of acute uncomplicated falciparum malaria were highlighted and suggestions on how to optimize the use of this drug were made.

Asexual and sexual stages of Plasmodium falciparum in Nigerian pregnant women attending antenatal booking clinic.

Susceptibility to infection by Plasmodium falciparum is increased in pregnant women. In sub-Saharan Africa, the consequences of maternal malaria include preterm birth, fetal growth restriction and increased infant mortality. Malaria transmission requires the circulation of viable gametocytes that can be ingested by the female mosquito taking a blood meal. This study was conducted to evaluate the presence of asexual and sexual stages of P. falciparum in pregnant women attending antenatal booking clinics in south-western Nigeria, an area hyper-endemic for malaria. Gametocyte carriage was about 13%, similar to that documented for children symptomatic for malaria in our area of study.

Use of Chloroquine in Uncomplicated Falciparum Malaria Chemotherapy: The Past; the Present and the Future

Chloroquine is a 4-aminoquinoline discovered over five decades ago for treatment of uncomplicated malaria. It was widely used as first line treatment and prophylaxis for individuals going into malaria endemic regions. It was initially highly effective against the four Plasmodium species (P. falciparum; P. malaria; P. ovale and P. vivax) infecting human. It is also effective against gametocytes except those of P. falciparum. Resistance of P. falciparum to chloroquine is widespread and led to discontinuation of chloroquine in malaria treatment by most countries. In recent times; evidences are emerging for chloroquine to probably secure its original place in treatment of acute uncomplicated falciparum malaria. This would be a welcome idea since chloroquine is readily available; relatively safer and cheaper than most currently use antimalarial drugs. Thus; researchers should intensify efforts on periodic in vitro monitoring of chloroquine efficacy; clinicians should further discourage use of chloroquine until efficacy is remarkably restored and pharmaceutical industries should look into potential chloroquine and chloroquine-resistance reversal fixed and non-fixed doses combinations

Pre-hospital and prescription use of antibacterial drugs at a secondary health centre in Ibadan, Nigeria

The overall goal of this study is to reduce morbidity and mortality ascribable to bacterial infections by encouraging rational use of antibiotics. Antibiotics use prior to and prescriptions of antibiotics by the attending physicians were evaluated in a group of patients attending a secondary health facility. A quasi-exit interview was conducted using a structured questionnaire. The major presenting symptoms were sought from patients and/or parents and/or guardians; drug history was taken and doctors' prescriptions were copied onto an already prepared format. All data were entered into EPI-INFO version 6 for analyses. The mean age of patients who were enrolled was 14 ±±±± 16.96 [range: 0.08-78 years] but males patients were statistically younger than females: respectively 9.94 ±±±± 15.48 years (0.08-78 years) and 18.43 ±±±±17.10 years (range: 0.08 ­ 70 years); F: 122 P< 0.00. Pre-hospital use of antibiotics was documented in about a third of all the patients and cotrimoxazole was the most commonly used antibiotics accounting for 68.5% of antibiotics use in this group patients. Antibiotics were contained in more than half of all the prescriptions and erythromycin and cephalosporin were antibiotics of choice. This is contrary to the previous findings in the same area of study but different health facility. There is need for formulation of appropriate drug policy and establishment of continuing medical education for doctors as well as public enlightenment programmes on rational use of antibiotics

Prescriptions involving analgesic drugs at a secondary health facility in ibadan, Nigeria.

INTRODUCTION: Pain is a cardinal feature of inflammation and is responsible for majority of hospital visits. The non-opioid analgesics possess antipyretic and anti-inflammatory activity and thus are often employed for such purpose of controlling inflammation as well as antipyretic. The non-opioid analgesics are freely available devoid of causing dependence but their potential harmful effects can sometimes be serious. The need for rational drug use is paramount and requires evaluation of physicians practice to serve as basis for continue medical education. METHODS: A retrospective assessment of pattern of prescription at a secondary health facility owned by one of the 36 states of the federation of Nigeria. The age, sex, the drugs prescribed per patient were recorded and prescriptions involving analgesics were further analyzed. Proportions were compared using X2 and statistical significance was set at p<0.05. RESULTS: Analgesic drugs were commonly prescribed constituting 23.8% of all the prescriptions recorded in the study. Paracetamol was the most commonly prescribed analgesic drug accounting for 55.7% of all analgesic drugs prescribed while Dipyrone was the most commonly prescribed parenteral analgesic drug. Dipyrone accounted for 19% of total Analgesic drug prescriptions but 93% of analgesics administered by intramuscular route. Dipyrone was also the preferred Analgesic drug in traumatic conditions. No cognizance was taken of the potential of NSAIDs for causing gastrointestinal injury as Diclofenac, Nimesulide and Dipyrone were sometimes used even in patients with peptic ulcer disease. CONCLUSIONS: Pain management with NSAIDs requires some dexterity in particular when certain categories of patients are to be treated. There is need for continue medical education to ensure rational use of these drugs.

Haematological profile of healthy pregnant women in Ibadan, south-western Nigeria.

There is a dearth of information on the reference values for haematological indices particularly according to the relevant trimesters of pregnant women in Nigeria. The objective of this study was to provide reference values for Nigerian pregnant women. The study took place at the Adeoyo Maternity Hospital and the University College Hospital, both in Ibadan. This descriptive study was carried out over a period of 8 months. Subjects were apparently healthy pregnant women that satisfied the inclusion and exclusion criteria. The mean values (and 95% confidence intervals, CI) of haematological indices were as follows -- First trimester: Haemoglobin (Hb) 112.44 (101.64 - 123.25) g/l, haematocrit (hct) 35 (32 - 38)%, WBC 5.488 (4.025 - 6.950) x 10(9)/l and platelet counts 227.56 (165.21 - 289.90) x 10(9)/l;Second trimester: Hb 100.39 (97.85 - 102.92) g/l, hct 29.3 (28.5 - 30.1)%, WBC 6.57 (6.19 - 6.95) x 10(9)/l, platelet count 229.56 (211.86 - 247.26); and the Third trimester: Hb 98.06 (96.12 - 100.00) g/l, hct 29.4 (28.7 - 29.9)%, WBC 6.92 (6.53 - 7.30), platelet count 186.52 (177.67 - 195.38) x 10(9)/l. These results were compared with those of 52 non-pregnant age matched women volunteers as controls whose mean haematological indices and 95% CI were: Hb 120.51 (116.61 - 124.41) g/l, hct 36 (25 - 48)%, WBC 5.28 (2.9 - 8.7) x 10(9), platelet count 330.87 (176 - 538) x 10(9)/l. The following haematological indices: WBC, platelet counts, RBC, PCT, and PDW, of women between the trimesters showed statistical significance (p value < 0.001 in each case). The WBC is inversely proportional to the PCT and the MCV in the pregnant women was slightly raised. In this study, pregnancy is characterised by lowest values of haemoglobin parameters in trimester three and there are statistically significant differences between the WBC, platelet counts, RBC, PCT, and PDW of women between the three trimesters.

Open randomized study of artesunate-amodiaquine vs. chloroquine-pyrimethamine-sulfadoxine for the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian children.

BACKGROUND: Artemisinin-based combination antimalarials are currently considered effective alternatives for the treatment of malaria in Africa, but there are few studies of such combinations in Nigerian children. We assessed the safety, treatment efficacy and effects on gametocyte carriage of the combination of artesunate plus amodiaquine and chloroquine plus pyrimethamine-sulfadoxine in children. METHODS: We evaluated 153 children who were aged 12 years or younger who had uncomplicated Plasmodium falciparum malaria. Patients were randomly assigned a combination of artesunate (4 mg/kg of body weight daily for 3 days) plus amodiaquine (30 mg/kg over 3 days), or chloroquine (25 mg/kg over 3 days) plus pyrimethamine-sulfadoxine (25 mg/kg of the sulfadoxine component at presentation). The primary endpoints were the proportions of children with adequate clinical and parasitological response, late parasitological failure, late clinical failure and early treatment failure. The parasitological cure rates on days 14-28 were also used as the primary endpoints. RESULTS: Both regimens were well tolerated; no child was withdrawn because of drug intolerance. All children treated with artesunate plus amodiaquine had adequate clinical and parasitological response (ACPR), while all but five children treated with chloroquine plus pyrimethamine-sulfadoxine had similar response. Fever clearance times were similar in the two treatment groups. However, the proportion of patients whose parasitaemia cleared by day 2 was significantly higher (100 vs. 50%, P = 0.00001) and parasite clearance was significantly faster (1.7 +/- 0.4 vs. 2.5 +/- 0.8 days, P = 0.0001) in children treated with artesunate plus amodiaquine. The cure rates on days 21 (100%vs. 94%, P = 0.03) and 28 (100%vs. 90%, P = 0.003) were also significantly higher in children treated with artesunate plus amodiaquine than in those treated with chloroquine plus pyrimethamine-sulfadoxine. Overall, a significantly higher proportion of children treated with chloroquine plus pyrimethamine-sulfadoxine carried gametocytes at least once during follow-up compared with those treated with artesunate plus amodiaquine [5 of 50 (10%) vs. 1 of 103 (0.97%), P = 0.01]. CONCLUSION: The combination of artesunate plus amodiaquine is therapeutically superior to a combination of chloroquine plus pyrimethamine-sulfadoxine, and significantly reduced gametocyte carriage following treatment.

Predictors of the failure of treatment with chloroquine in children with acute, uncomplicated, Plasmodium falciparum malaria, in an area with high and increasing incidences of chloroquine resistance.

Resistance to chloroquine (CQ) in Plasmodium falciparum has reached unacceptably high levels in many endemic countries. The pre-treatment factors that identify the children who are at risk of treatment failure after being given CQ were evaluated in 385 children with acute, uncomplicated, Plasmodium falciparum malaria. These children each took part in one of six antimalarial drug trials conducted, between July 1996 and July 2004, in a hyper-endemic area of south-western Nigeria. Following treatment with CQ, 149 (39%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =7 years [giving an adjusted odds ratio (AOR) of 2.17, with a 95% confidence interval (CI) of 1.19-3.85; P = 0.01], an asexual parasitaemia of > or =100,000/microl (AOR = 2.17; CI = 1.08-4.35; P = 0.03), the presence of gametocytaemia (AOR = 2.08; CI = 1.14-3.85; P = 0.02) and enrolment >4 years after commencement of the study (i.e. after 2000; AOR = 2.13; CI = 1.3-4.0; P = 0.003) were found to be independent predictors at presentation of the subsequent failure of treatment with CQ. Compared with the other children, those who failed to clear their parasitaemias within 3 days and those who still had fever 1-2 days after commencing treatment were more likely to be treatment failures. Together, these findings may have implications for malaria-control efforts in all areas of sub-Saharan Africa where treatment of malaria depends almost entirely on antimalarial monotherapy.