The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

Diagnostic accuracy of Xpert MTB/RIF Ultra for childhood tuberculosis in West Africa - a multicenter pragmatic study.

OBJECTIVE: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems. METHODS: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. RESULTS: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0-79.0%) and 95.0% (95% CI: 88.0-98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6-83.3%) and 70.9% (95% CI: 51.9-85.8%), respectively. CONCLUSION: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries.

First-line antituberculosis drugs disrupt endocrine balance and induce ovarian and uterine oxidative stress in rats.

BACKGROUND: The first-line antituberculosis (anti-TB) drugs, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA), are effective in the treatment of pulmonary tuberculosis. However, the toxicity of these drugs in the clinical setting limits their use. Here, we evaluated the effects of anti-TB drugs on the reproductive system in female rats. METHODS: Thirty-five female Wistar rats were assigned into five groups of seven animals each. The control group received normal saline, whereas others received INH (5 mg/kg), RIF (10 mg/kg), EMB (15 mg/kg), and PZA (15 mg/kg) through gavage thrice a week for 8 consecutive weeks. RESULTS: Administration of anti-TB drugs significantly (p<0.05) reduced uterine and ovarian weight, as well as the relative weight of the uterus when compared with controls. In addition, anti-TB drugs increased the activities of alanine aminotransferase as well as the level of total bilirubin. Treatment with INH, RIF, and PZA significantly (p<0.05) reduced the levels of follicle-stimulating and luteinizing hormones, estrogen, and prolactin. The INH, RIF, EMB, and PZA caused significant (p<0.05) increases in uterine malondialdehyde (MDA) levels by 281%, 214%, 273% and 190%, respectively, whereas INH and EMB increased the ovarian malondialdehyde by 111% and 129%, respectively. These drugs significantly (p<0.05) decreased the activities of ovarian glutathione-S-transferase and uterine glutathione peroxidase, superoxide dismutase, and catalase. Histology revealed the erosion of uterine mucosa, debris in the lumen of the uterus, congestion, and underdeveloped follicles in ovaries. CONCLUSIONS: The first-line anti-TB drugs elicited reproductive toxicity in the uterus and ovaries of rats through mechanisms that involved oxidative stress.

Ameliorative Effects of Kolaviron, a Biflavonoid Fraction from Garcinia Kola Seed, on Hepato-renal Toxicity of Anti-tuberculosis Drugs in Wistar Rats.

BACKGROUND: Tuberculosis (TB) is an infectious disease of international health priority. The combination of anti-TB drugs (4-Tabs)- isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (ETB) are effective in the management of the disease, however, their toxic effect is a major concern. PURPOSE: The study was designed to evaluate the toxicity of anti-TB drugs in male Wistar rats and possible ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola seeds. METHODS: Twenty-eight rats were assigned into four groups; Group 1 (Control) received corn oil, Group 2 (4-Tabs) received therapeutic doses of INH (5 mg/kg), RIF (10 mg/kg), PZA (15 mg/kg) and ETB (15 mg/kg) in combination, Group 3 (4-Tabs + KV) received INH, RIF, PZA, ETB and KV (200 mg/kg) and Group 4 (KV) received KV (200 mg/kg) by oral gavage three times per week for 8 consecutive weeks. RESULTS: Administration of 4-Tabs caused oxidative stress resulting in significant (p = 0.031, 0.027) increase in malondialdehyde levels in the liver and kidney of rats by 101% and 34%, respectively. Also, 4-Tabs caused significant (p = 0.023-0.035) elevation of serum alanine and aspartate aminotransferases by 41% and 48%, creatinine by 252% and total bilirubin by 89%, respectively. In contrast, hepatic and renal antioxidant indices- reduced glutathione, glutathione peroxidase, glutathione-s-transferase and superoxide dismutase were significantly (p = 0.028-0.039) decreased in 4-Tabs-treated rats. Co-administration of KV with 4-Tabs significantly restored the antioxidant parameters and biochemical indices to near normal. CONCLUSION: These findings suggest that anti-TB drugs elicit oxidative damage in liver and kidney of rats while KV protects against the adverse effects via antioxidative mechanism.

Diagnosis of tuberculosis: urgent need to strengthen laboratory services.

Tuberculosis (TB) is of great public health concern globally, and the impact is most felt in developing countries of Asia and Africa, where 95% of cases and 98% of deaths are attributable to the disease, The disease is poverty-driven and the situation is further worsened by absence of rapid diagnostic tools to facilitate early diagnosis of the illness, thus leading to widespread of the disease. While attention is being focused on the HIV/AIDS pandemic, little is being heard of TB, especially in the areas of laboratory diagnosis despite the fact that the disease is the commonest cause of death in people living with HIV/AIDS. The importance of a diagnostic laboratory in a TB control program cannot be overemphasized. Smear microscopy, which is the cornerstone of World Health Organization (WHO) 'DOTS' strategy for the treatment of TB, has many drawbacks among which is its inability to detect latent infection and the dependency of its sensitivity on a trained and motivated microscopist. Therefore, there is a need for a more reliable, sensitive and rapid diagnostic test to facilitate early diagnosis of cases and prompt initiation of therapy for a TB control program to have a meaningful impact in the community.

Prevalence of STI/HIV co-infections among special treatment clinic attendees in Ibadan, Nigeria.

Sexually transmitted infections (STIs) are poorly recognised and inadequately treated in Nigeria despite the fact that they constitute a major risk factor for sexual transmission of HIV infection. This study was carried out to ascertain STI/HIV co-infection rates and also to obtain relevant socio-demographic and reproductive health data associated with STI/HIV infections among special treatment clinic (STC) attendees. This information is urgently needed for designing STI/HIV control strategies. All consenting patients who attended the STC clinic from March to November 2001 were interviewed to obtain their socio-demographic and reproductive health data. Urethral, high vaginal and endocervical swabs and urine specimens were obtained and processed by standard methods. HIV screening was done by double ELISA tests. Of the 210 patients seen, 98 (46.7%) were male and 112 (53.3%) were female (p > 0.05). The majority, 171 (81.4%) were aged 20-39 years, while only ten (4.8%) were adolescents. One-hundred-and-eighty (85.7%) had an STI, of which 41 (22.8%) were co-infected with HIV. Thirty (16.7%) patients with nongonococcal urethritis/cervicitis and five (2.8%) with gonorrhoea were also positive for HIV. Five patients were HIV positive but had no other STI. Patients with gonorrhoea, non-gonococcal urethritis/cervicitis, trichomoniasis and bacterial vaginosis were more likely than those with warts, candidiasis and herpes to have co-infection (chi2 = 12.5, p = 0.04). The study's HIV prevalence rate was 21.9%. STI/HIV co-infection rate was significantly higher among unskilled and unemployed patients compared with professional and skilled workers (p < 0.05). This study shows a high STI/HIV co-infection rate indicating that there is need for proper management of STI, as this will help curb the spread of HIV infection in Nigeria.

Biofilm formation by Mycobacterium bovis: influence of surface kind and temperatures of sanitizer treatments on biofilm control.

Mycobacterium bovis causes classic bovine tuberculosis, a zoonosis which is still a concern in Africa. Biofilm forming ability of two Mycobacterium bovis strains was assessed on coupons of cement, ceramic, or stainless steel in three different microbiological media at 37°C with agitation for 2, 3, or 4 weeks to determine the medium that promotes biofilm. Biofilm mass accumulated on coupons was treated with 2 sanitizers (sanitizer A (5.5 mg L(-1) active iodine) and sanitizer B (170.6 g(1) alkyl dimethylbenzyl ammonium chloride, 78 g(-1) didecyldimethyl ammonium chloride, 107.25 g L(-1) glutaraldehyde, 146.25 g L(-1) isopropanol, and 20 g L(-1) pine oil) at 28 and 45°C and in hot water at 85°C for 5 min. Residual biofilms on treated coupons were quantified using crystal violet binding assay. The two strains had a similar ability to form biofilms on the three surfaces. More biofilms were developed in media containing 5% liver extract. Biofilm mass increased as incubation time increased till the 3rd week. More biofilms were formed on cement than on ceramic and stainless steel surfaces. Treatment with hot water at 85°C reduced biofilm mass, however, sanitizing treatments at 45°C removed more biofilms than at 28°C. However, neither treatment completely eliminated the biofilms. The choice of processing surface and temperatures used for sanitizing treatments had an impact on biofilm formation and its removal from solid surfaces.

Significant bacteriuria among asymptomatic antenatal clinic attendees in ibadan, Nigeria.

Untreated asymptomatic bacteriuria can lead to urinary tract infection (UTI) in pregnancy with devastating maternal and neonatal effects such as prematurity and low birth weight, higher fetal mortality rates and significant maternal morbidity. We carried out a two year (April 2007 to March 2009) cross-sectional epidemiological study to determine the prevalence of significant bacteriuria among asymptomatic antenatal clinic attendees at two antenatal clinics (ANCs) in University College Hospital and Adeoyo Maternity Hospital, both in Ibadan, Nigeria.All consenting ANC attendees without UTI were enrolled in the study. Urine specimens of 5 to 10 ml collected from each subject were examined microscopically for white blood cells, red blood cells and bacteria. The specimens were further cultured on MacConkey agar using a sterile bacteriological loop that delivered 0.002 ml of urine. Colony counts yielding bacterial growth of more than 10(5)/ml of pure isolates were considered significant.Of the 473 subjects studied, 136 had significant bacteriuria, giving a prevalence rate of 28.8%. The highest age specific prevalence (47.8%) was found in the 25-29 year olds while only one (0.7%) was found in the teenage group. A large percentage (64.0%) of subjects with significant bacteriuria had tertiary education, compared with 4.4% who had no formal education but the association was not statistically significant (X(2) = 0.47, p = 0.79). The majority (75.8%) of subjects with significant bacteriuria had no previous history of abortion, while 20 (14.7%) had one previous abortion and only three (2.1%) admitted to three previous abortions (X(2) = 5.16, p = 0.16). The majority (69.8%) of those with significant bacteriuria presented at second trimester while 38 (28.0%) presented at third trimester (X(2) = 6.5, p = 37).Only 22 (4.6%) of the studied subjects presented at first trimester, and 3 (13.7%) of these had significant bacteriuria.The prevalence of asymptomatic bacteriuria is high among this study population. Hence we suggest that advocacy programs be initiated to urge pregnant women to access ANC services early in pregnancy.

Effect of face washing with soap and water and cleaning with antiseptics on upper-lid bacteria of surgical eye patients.

OBJECTIVE: To determine the effect of face washing with soap and water and cleaning with povidone iodine and cetrimide/chlorhexidine gluconate (Savlon) on upper-lid bacteria. DESIGN: Prospective, nonrandomized clinical trial. PARTICIPANTS: Eighty patients attending the Eye Clinic, University College Hospital, Ibadan, Nigeria. METHODS: Eighty patients assigned to 4 groups had swabs of the upper eyelid skin taken before and after face wash with soap and water, and cleansing with Savlon and 5% povidone iodine. Specimens were cultured and Gram stained. Bacterial counts were carried out using standard techniques. RESULTS: Face washing with soap and water increased the proportion of patients with bacterial isolates from 80.0% to 87.5%. The average colony count increased from 187.1 to 318.5 colony units per mL (p = 0.02). Application of 5% povidone iodine without face washing with soap and water reduced the proportion of patients with bacterial isolates from 82.6% (mean count 196.5) to 28.6% (mean count 34.1)(p = 0.001); in comparison, the application of 5% povidone iodine after face washing with soap and water reduced the proportion from 71.4% (mean count 133.9) to 40.0% (mean count 69.0)(p = 0.01). Application of Savlon without face washing with soap and water reduced the proportion of patients with bacterial isolates from 100% (mean count 310.9) to 41.2% (mean count 19.8)(p = 0.004) compared with the application after face washing, which reduced the proportion from 89.5% (mean count 240.3) to 41.2% (mean count 82.9)(p = 0.02). CONCLUSIONS: Both povidone and Savlon are effective in reducing periocular bacteria in an African setting. Prior face washing with soap and water had no added benefit in reducing bacterial colony count.