Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis.

In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months. Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed. The bacteriological response was assessed by culture conversion in liquid and solid media. Geometric mean total exposures (area under the concentration-versus-time curve up to 24 h after the dose) were 24.6, 50.8, and 76.1 mg · h/liter in the 600-mg, 900-mg, and 1,200-mg groups, respectively, reflecting a nonlinear increase in exposure with the dose (P < 0.001). Grade 3 adverse events occurred in only 2 patients in the 600-mg arm, 4 patients in the 900-mg arm, and 5 patients in the 1,200-mg arm. No significant differences in the bacteriological response were observed. Higher daily doses of rifampin (900 and 1,200 mg) resulted in a more than proportional increase in rifampin exposure in plasma and were safe and well tolerated when combined with other first-line anti-TB drugs for 2 months, but they did not result in improved bacteriological responses in patients with pulmonary TB. These findings have warranted evaluation of even higher doses of rifampin in follow-up trials. (This study has been registered at ClinicalTrials.gov under identifier NCT00760149.).

Light-emitting diode with various sputum smear preparation techniques to diagnose tuberculosis.

SETTING: Mawenzi Regional Hospital, northern Tanzania. OBJECTIVE: To determine the value of light-emitting diode (LED) microscopy in diagnosing tuberculosis (TB) on bleach-treated and direct sputum smears. DESIGN: Sputum samples were collected from patients suspected of pulmonary TB who presented consecutively at the laboratory for smear evaluation between December 2009 and February 2010. Four smears were prepared from each specimen: conventional Ziehl-Neelsen (ZN), direct auramine, bleach centrifugation and bleach short sedimentation auramine smears. A light microscope was used to examine ZN smears and an LED fluorescent microscope to examine auramine-stained smears. RESULTS: Of the 267 sputum samples examined, respectively 78 (29%), 62 (23%), 74 (28%) and 48 (18%) were acid-fast bacilli (AFB) positive by the bleach centrifugation, bleach short sedimentation, direct auramine and ZN methods. Bleach centrifugation identified 30 (11%) more positives than ZN microscopy (P < 0.001), but was not superior to the direct auramine method (P = 0.46), which yielded 26 (10%) more positives than ZN microscopy (P < 0.001). Fluorescent LED required a shorter smear reading time (1.5 min on average), while the light microscope took 4 min (P < 0.001). CONCLUSION: Fluorescent LED microscopy with direct smear preparation is rapid and effective. Further studies are needed to ascertain its performance under routine conditions.

Serum 25-hydroxy-vitamin D3 concentrations increase during tuberculosis treatment in Tanzania.

SETTING: Vitamin D deficiency is associated with susceptibility to active tuberculosis (TB) in many settings. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs, isoniazid and rifampicin, reduce 25-hydroxy vitamin D (25[OH]D) concentrations. OBJECTIVE: To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB (PTB). DESIGN: We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment. RESULTS: Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment (median increase 6.0 nmol/l, IQR -0.7-25.0, P = 0.001). Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l (median increase 0.46, IQR -0.2-1.1, P < 0.001). CONCLUSION: 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania. Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations.

Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.

SETTING: Kilimanjaro Region, northern Tanzania. OBJECTIVE: To assess the effect of the introduction of the patient-centred tuberculosis treatment (PCT) approach-which allows tuberculosis (TB) patients to choose between community and facility-based directly observed treatment (DOT)-on treatment outcomes, and to analyse factors that contribute to opting for community DOT. DESIGN: Retrospective analysis of treatment outcomes of TB patients registered in the Kilimanjaro Region in 2007, differentiating between patients under community vs. facility-based DOT and taking into account demographic factors, disease classification, TB diagnosis and human immunodeficiency virus (HIV) status. RESULTS: Data from 2769 TB patients were analysed. Treatment success rates were respectively 81% and 70% in patients under community vs. facility-based DOT (P < 0.001). Cure rates were respectively 73% and 72% in smear-positive pulmonary TB patients under community vs. facility-based DOT (P = 0.62). Women, children, patients residing in districts other than Hai, patients with newly diagnosed TB and patients with smear-negative pulmonary TB were most likely to be under community DOT. CONCLUSION: The PCT approach was shown to be effective in terms of treatment outcomes. Treatment success rates were higher in patients who opted for community DOT than in patients who chose facility-based DOT (all cases), and were similar in smear-positive pulmonary TB patients under community or facility-based DOT.

Aetiology and presentation of HIV/AIDS-associated pulmonary infections in patients presenting for bronchoscopy at a referral hospital in northern Tanzania.

OBJECTIVES: To determine the aetiological agents of pulmonary infections in HIV-infected Tanzanians and to correlate the causative agents with clinical, radiographic features, and mortality. DESIGN: A prospective study. SETTING: Kilimanjaro Christian Medical Centre (KCMC), Tanzania. SUBJECTS: Bronchoalveolar lavage fluid (BAL) were obtained from 120 HIV infected patients with pulmonary infections. BAL for causative agents was analysed and correlated with clinical and radiographic features, and one-month outcome. RESULTS: Causative agents were identified in 71 (59.2%) patients and in 16 of these patients, multiple agents were found. Common bacteria were identified in 35 (29.2%) patients, Mycobacterium tuberculosis in 28 (23.3%), Human Herpes Virus 8 (HHV8) in 12 (10%), Pneumocystis jiroveci in nine (7.5%) and fungi in five (4.2%) patients. Median CD4 T cell count of the patients with identified causes was 47 cells/microl (IQR 14-91) and in the 49 patients with undetermined aetiology was 100 cells/ microl (IQR 36-188; p = 0.01). Micronodular chest radiographic lesions were associated with presence of M. tuberculosis (p = 0.002). The one-month mortality was 20 (16.7%). The highest mortality was associated with HHV8 (41.7%) and M. tuberculosis (32.1%). Mortality in patients with undetermined aetiology was 11.3%. No death occurred in patients with PCP. CONCLUSION: In this population of severely immunosuppressed HIV-infected patients with pulmonary infection a variety of causative agents was identified. Micronodular radiographic lesions were indicative of TB. High mortality was associated with M. tuberculosis or HHV8. No death occurred in patients with P. jiroveci infection.

Bronchoalveolar neutrophils, interferon gamma-inducible protein 10 and interleukin-7 in AIDS-associated tuberculosis.

During advanced AIDS tuberculosis (TB) often presents atypically with smear-negative and non-cavitary disease, yet immune features associated with this change are poorly characterized. We examined the local immune response in a cohort of Tanzanian AIDS-associated TB patients who underwent bronchoalveolar lavage. TB infection was confirmed in bronchoalveolar lavage (BAL) fluid by culture, probe and polymerase chain reaction (PCR). Among TB patients CD4 count correlated positively with the extent of cavitary disease as well as BAL TB load (qPCR C(T)). TB patients had significantly higher granulocyte-macrophage colony-stimulating factor (GM-CSF) than non-TB patients, and those with non-cavitary TB had significantly higher BAL interferon gamma-inducible protein (IP-10) and interleukin (IL)-7 than those with cavities. BAL neutrophils were as prevalent as monocytes/macrophages or epithelial cells, and immunohistochemistry revealed that neutrophils, monocytes/macrophages, and epithelial cells were major sources of the IP-10 and IL-7. These data suggest a dysregulated cytokine profile may contribute to the TB of advanced AIDS.

Transverse myelitis due to trypanosomiasis in a middle aged Tanzanian man.

We report the case of a middle aged Tanzanian man who developed a spinal cord syndrome over 6 weeks, along with a mild encephalopathy. Investigations ruled out the usual major causes of such a syndrome in our setting in northern Tanzania. Examination of his cerebrospinal fluid revealed trypanosomes, and he made a slow but dramatic improvement after a full course of suramine and melarsoprol. We postulate that he had a transverse myelitis due to African trypanosomiasis, a rare and barely recognised cause.

Hookworm infection of the duodenum associated with dyspepsia and diagnosed by oesophagoduodenoscopy: case report.

Hookworm infection and peptic ulcer disease are common in subtropical and tropical countries. While hookworm infection is endemic where sanitary conditions are poor, peptic ulcer disease is associated with a high prevalence of Helicobacter pylori infection. Dyspepsia and epigastric pain are common presenting symptoms of patients with either hookworm infection or peptic ulcer disease. Consequently it is common practice at our healthcare facility to examine stool for ova or parasites before considering empirical gastric acid suppressive therapy or Helicobacter pylori eradication therapy. We describe a patient who presented with dyspepsia and epigastric pain whose stool examination showed no ova or parasites. The patient's symptoms did not improve with proton pump inhibitor therapy. Endoscopy revealed hookworms in the first part of the duodenum. We review published reports of hookworms at this location. In hookworm endemic areas, when empirical treatment for dyspepsia and upper abdominal pain with acid suppressive agents does not offer remedy, antihelminthic agents should be considered even when stool for ova or parasites is negative.

HIV-associated morbidity, mortality and diagnostic testing opportunities among inpatients at a referral hospital in northern Tanzania.

Hospitalized patients with HIV infection are among the most likely to benefit from the expanding availability of anti-retroviral therapy in sub-Saharan Africa. Between 1990 and 2000, 3667 people known to be HIV-infected were admitted to Kilimanjaro Christian Medical Centre (KCMC) in Moshi, northen Tanzania. The level of inpatient mortality among these patients varied from 15%-21%, and the proportion of the HIV-infected patients admitted who were female increased significantly, from 45% at the start of the study period to 52% at the end (P <0.001). When the medical records for 1683 of the HIV-infected patients who had been admitted between 1996 and 2001 were reviewed, the most prevalent diagnoses on admission were found to be pulmonary tuberculosis (21%), malaria (14%) and gastro-enteritis/diarrhoea (12%) among the adults, and non-tubercular pulmonary infection (21%), pulmonary tuberculosis (19%) and gastro-enteritis/diarrhoea (12%) among the children. The crude odds ratios (OR) for inpatient death were greatest for adults presenting with meningitis [OR=3.7; 95% confidence interval (CI)=2.1-6.7], septicaemia (OR=2.9; CI=1.2-7.3) or renal disease (OR=2.6; CI=1.2-5.7), and mortality was higher for men than for women (OR=1.4; CI=1.1-1.8). A single-day, point-prevalence survey in September 2001, among the KCMC's inpatients, identified HIV infection in 21% of those surveyed, many (44%) of the patients found positive being previously unaware of their infection. HIV infection remains a major cause of hospitalization and mortality in Moshi. A policy of routine testing would increase the number of HIV infections detected, allowing improvements in case management and in the prevention of infection.

Hepatosplenic schistosomiasis: a review.

BACKGROUND: Schistosomiasis is a granulomatous disease that is caused by infection with schistosomes. It is a major health threat in tropical and subtropical countries. Due to increased movement, all residents of the universe are at risk of contracting this infection. The infection goes through several stages, but the most life-threatening form and leading cause of mortality is hepatosplenic schistosomiasis (HSS). It is a chronic complication, which develops as a consequence of inflammatory response. This complication has not been adequately addressed or attended the and as a consequence most of patients presenting with this complication in our settings die. OBJECTIVES: To review literature on hepatosplenic schistosomiasis, to give the state-of-the-art management of HSS, to give our own experience on management of this complication and hence impart knowledge to medical personnel on HSS. DATA SOURCE: Literature is from Medline database and experience from gastroenterology clinics. Our own experience has been blended on top. STUDY SELECTION AND DATA EXTRACTION: We have selected material, which have been verified and can be applicable in resource poor-countries, where this problem is a major health threat. DATA SYNTHESIS: Based on published studies and meta-analyses and our own experience we have been able to draw conclusions on the current understanding of the subject. CONCLUSION: Hepatosplenic schistosomiasis is a deadly complication and occurs mainly in poor countries. Regular reviews and updates of our knowledge is important to enable stakeholders of health sector understand the problem and develop strategies on its management.