ABSTRACT
Amodiaquine (AQ), an effective antimalarial drug for uncomplicated malaria, has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety, tolerability, and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3% CQ treated-aparasitaemic, 23.8% of CQ treated-parasitaemic, 28.6% ofAQ-treated parasitaemic and 14.3% of aparasitaemic receiving AQ. Amodiaquine attained 100% parasitological clearance rate versus 70% in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects.
Subject(s)
Amodiaquine/adverse effects , Antimalarials/adverse effects , Chloroquine/adverse effects , Malaria, Falciparum/drug therapy , Adolescent , Adult , Agranulocytosis/chemically induced , Amodiaquine/administration & dosage , Analysis of Variance , Animals , Antimalarials/therapeutic use , Chemical and Drug Induced Liver Injury , Chloroquine/administration & dosage , Humans , Liver/drug effects , Malaria, Falciparum/blood , Malaria, Falciparum/parasitology , Male , Middle Aged , Tanzania , Treatment Outcome , Young AdultABSTRACT
Amodiaquine (AQ); an effective antimalarial drug for uncomplicated malaria; has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety; tolerability; and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3CQ treated-aparasitaemic; 23.8of CQ treated-parasitaemic; 28.6of AQ-treated parasitaemic and 14.3of aparasitaemic receiving AQ. Amodiaquine attained 100parasitological clearance rate versus 70in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects
Subject(s)
Amodiaquine/adverse effects , Antimalarials , Chloroquine/adverse effects , Malaria/therapy , Plasmodium falciparumABSTRACT
Pulmonary tuberculosis diagnosis commonly relies on the bacteriological examination of sputum. A cross-sectional hospital-based study was carried out to compare on "on the spot" sputum staining using sodium hypochlorite (bleach method) and routine Ziel-Neelsen (ZN) staining technique. Study candidates included individual patients presenting with cough <3 weeks (Group I) and > or =3 weeks (Group II). Sensitivity and specificity of the bleach method was calculated and compared at 100% using the ZN staining technique as the standard. A total of 171 patients (94 males, 77 females) with mean age 34.9 years (SD +/- 12.9) were recruited. Fifty-eight patients had coughed for <3 weeks while 113 had coughed for 23 weeks. Smear-positive TB in Group I was 13.8% (95% CI = 5-23) while in Group II was 25.7% (95% CI = 21-29). Using the bleach method, the prevalence of smear-positive TB in Group II was 28.3% (CI 95% = 20-36). This was an increase in smear-positivity rate of 15.6% as compared to the ZN technique. These results suggest that the use of bleach technique "on the spot" improve the sensitivity of tuberculosis diagnosis among patients with a history of coughing of over three weeks. However, further studies in different settings are recommended to validate the technique.
Subject(s)
Microscopy , Sodium Hypochlorite , Tuberculosis, Pulmonary/diagnosis , Adult , Female , Humans , Male , Middle Aged , TanzaniaABSTRACT
Pre and post-diethylcarbamazine treatment clinical expression, microfilaraemia prevalence and cellular responses were investigated in individuals in Tanga, Tanzania. Fifty-seven male individuals (aged = 15 years old) were identified for further studies on IL-4, IL-6, IL-8. IFN-gamma, IL-beta, TNF-alpha and nitric oxide in plasma and hydrocoele fluid. Microfilarial prevalence in the examined individuals was 12% with a geometric mean intensity (GMI) of 838 mff/ml in a community with a population of 1018 individuals. Microfilaraemic hydrocoele stage II and III were the most frequent pathologies observed with prevalence of 17.5% and 42. 1 %, respectively. All study individuals treated with diethylcarbamazine (DEC) standard dose of 6 mg/kg experienced post-treatment adverse events. There was no direct relationship between elevated IL-6 and the occurrence and severity of clinical adverse effects post-treatment. The findings from this study suggests that, blood elevated cytokine profile is not the main etiological factor in the inflammatory responses developing after treatment of bancroftian filariasis infections and pathology with DEC. Plasma levels of cellular (cytokines) responses during treatment revealed a proportion of symptomatic patients. Prior to treatment, patients with hydroecoele had high levels of IL-6 than those without the pathology. In conclusion these findings do not support the hypothesis that pro-inflammatory cytokines are directly responsible for adverse events to DEC chemotherapy in bancroftian filariasis infections and pathologies such as hydrocoele, lymphoedema and elephantiasis.
Subject(s)
Diethylcarbamazine/therapeutic use , Elephantiasis, Filarial/drug therapy , Filaricides/therapeutic use , Wuchereria bancrofti/pathogenicity , Adolescent , Animals , Diethylcarbamazine/adverse effects , Elephantiasis, Filarial/blood , Elephantiasis, Filarial/immunology , Female , Filaricides/adverse effects , Humans , Interleukin-6/blood , Male , Wuchereria bancrofti/isolation & purificationABSTRACT
A hospital based open-label clinical trial of 19 apparently healthy adult males with microfilaraemia was conducted to assess safety, tolerability and efficacy of doxycycline on Wuchereria bancrofti. Study individuals were assigned 8 weeks treatment with doxycycline 200 mg daily. The results of different selected tests showed that, the haematological, hepatic, renal and clinical parameters pre-and post-drug administrations were within the normal range for all treated individuals. Clinical adverse events were mild, transient, tolerable and reported in 7/19 (36.8%) of the study cohort. The mf clearance rate was 100% at 12 months post treatment for the 13 individuals who completed the follow up. These findings indicate that, although the drug was administered for a long period, there was no evidence of toxicity to the myocardium, hepatocytes, renal, bone marrow and blood cells, suggesting that an 8-week course of 200 mg/day doxycycline is a safe and tolerable regime for the treatment of Wuchereria bancrofti infections.
Subject(s)
Doxycycline/administration & dosage , Filariasis/drug therapy , Wuchereria bancrofti/drug effects , Administration, Oral , Adolescent , Adult , Aged , Animals , Doxycycline/adverse effects , Doxycycline/therapeutic use , Drug Evaluation , Drug-Related Side Effects and Adverse Reactions , Filariasis/microbiology , Humans , Male , Middle Aged , Tanzania , Wuchereria bancrofti/pathogenicitySubject(s)
Doxycycline , Doxycycline/adverse effects , Drug Tolerance , Safety , Treatment Outcome , Wuchereria bancrofti/therapyABSTRACT
We investigated the expression of intercellular adhesion molecule 1 (ICAM-1) in malarial placenta and related histological changes. Thirty-two malarial and 40 control term placentae were collected at Tanga, Tanzania and examined histologically and immunohistochemically. Malaria infected placentae were further divided into acute (15) and chronic (17) cases according to the presence of malarial pigment. The expression of ICAM-1 on monocyte, syncytio- and cytotrophoblasts, endothelial and stromal cells was assessed. Birthweight was lower and leukocyte counts higher in placentae with chronic infection. Many monocytes were present within the intervillous spaces, especially in placentae with chronic infection, and aggregated with parasitized erythrocytes. Some monocytes were adhesive to the surface of fibrinoid deposits. ICAM-1 expression on monocytes of malarial placentae was significantly conspicuous and correlated to the degree of intervillous leukocyte infiltration. Syncytiotrophoblasts often did not show ICAM-1, even though ICAM-1 was expressed by endothelium and weakly by cytotrophoblasts and stromal cells in both infected and control placentae. These results suggest that the expression of ICAM-1 on monocytes contributes to sequestration of infected erythrocytes within the intervillous spaces and their adhesion to fibrin masses and that ICAM-1 is unlikely to be associated with the direct adhesion of infected erythrocytes to the syncytiotrophoblasts.
Subject(s)
Intercellular Adhesion Molecule-1/analysis , Malaria, Falciparum/metabolism , Placenta/chemistry , Placenta/parasitology , Pregnancy Complications, Parasitic/metabolism , Birth Weight , Cell Adhesion , Endothelium/chemistry , Erythrocytes/parasitology , Erythrocytes/physiology , Female , Humans , Immunohistochemistry , Leukocyte Count , Monocytes/chemistry , Monocytes/pathology , Placenta/pathology , Pregnancy , Stromal Cells/chemistry , Trophoblasts/chemistry , Trophoblasts/pathologyABSTRACT
To assess the significance of lymphatic filariasis for the development of chronic genital manifestations and for reproductive health in women, we conducted a cross-sectional study of 2 villages in north-eastern Tanzania including interview and gynaecological examination of adult women, focusing primarily on reproductive history and genital health. In a population of 2165 residents, prevalence of Wuchereria bancrofti microfilaraemia was 28%, and geometric mean intensity of microfilariae (mf) was 722 mf/mL. Leg lymphoedema (elephantiasis) was present in 4.2% of adults aged > or = 15 years, and hydrocoele in 26.5% of adult males. Five hundred and thirty women completed an interview, and 404 of these completed a gynaecological examination. Most women were Muslims (72%), polygamy was common (29%), and 49% of women had undergone circumcision (clitoridectomy). Presence of microfilaraemia did not influence fertility or fertility-related variables including age at menarche, parity, spontaneous abortion, stillbirth, Caesarean section and premature labour, nor presence of primary or secondary infertility. Mf status was strongly correlated with abnormal menstruation pattern in the 30+ years age-group (P = 0.001), but not in the < 30 years age-group. Cervical, vaginal and vulval pathology was unrelated to mf status. Two women, aged 46 and 77 years, had vulval oedema of probable filarial origin, both were mf negative. Overall, microfilaraemia appeared to have no influence on genital disease or reproductive health, and chronic manifestations of lymphatic filariasis of the genitals does not appear to be a substantial problem in women.