Genotyping and molecular detection of multidrug-resistant Mycobacterium tuberculosis among tuberculosis lymphadenitis cases in Addis Ababa, Ethiopia.

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major public health problem. Drug-resistance surveillance data show that 3.9% of new and 21% of previously treated TB cases were estimated to have had rifampicin/ multidrug-resistant tuberculosis (MDR/RR-TB) in 2015. This implies that the MDR-TB is increasing alarmingly. Hence, a better understanding of drug resistance mechanisms and genotypes associated with multidrug resistance in M. tuberculosis is crucial for improving diagnostic and therapeutic methods to treat individuals with MDR-TB. The aim of this study was to analyze molecular drug resistance mutations of MDR-TB isolates from the cases of TB-lymphadenitis in relation to its genetic lineages. A cross-sectional study was conducted on culture positive cases from July to October, 2014 in Addis Ababa, Ethiopia. Sixty isolates were included to analyze drug resistance mutated gene responsible for MDR-TB in relation to its molecular genotyping. Mycobacterial culture, GenoTypeMTBDR plus and Spoligotyping were used to undertake the study. Of 60 TBLN isolates, 8.3% were identified MDR-TB cases and one isolate was isoniazid mono-resistant. Eleven isolates in T3-ETH genetic sub lineage were sensitive to both RMP and INH, while only 2 isolates were MDR-TB. Most of the RMP- resistant isolates showed mutation in codon S531L and all isolates mutated in the katG gene conferring INH resistant strains had mutations in codon of S315T1. Screening for the rpoB and katG gene mutation of tuberculosis lymphadenitis is useful in Ethiopia for an early detection and treatment of MDR-TB. Besides, there is a drug resistance variation among different lineages of Tuberculosis lymphadenitis which has important consequences for the development of efficient control strategies.

Dynamics of impairment during and after treatment: the AMFES cohort.

This study investigates the dynamics of impairment during and after multidrug therapy treatment for the patient cohort of the prospective ALERT MDT Field Evaluation Study (AMFES). The impairment status was compared at intake, at release from treatment (rft), and at the time of the latest survey between 24 and 48 months after release from treatment (follow-up). The eye-hand-foot impairment score (EHF score), which is the sum of the WHO impairment grades of the eyes, hands, and feet, was used as tool for comparison. In all, 433 out of the 592 patients (224 PB and 209 MB) completed treatment in time and were assessed at release from treatment. The risk of getting impaired was 4% for the 113 PB and 21% for the 91 MB patients who were initially free from impairment. Out of the 111 initially impaired PB patients, 41% recovered or improved and 13% worsened in EHF score. For the 118 initially impaired MB patients, these figures were: recovery or improvement 43% and worsening 13%. Three hundred and twenty-three out of the 433 patients (158 PB and 165 MB) had a follow-up examination in between the next 24-48 months after rft. The risks of impairment at follow-up were 6% for the 79 PB and 18% for the 77 MB patients without impairment at rft. Out of the 79 PB patients with impairment at rft, 35% recovered or improved and 28% worsened. For the 88 impaired MB patients, these figures were: recovery or improvement 26% and worsening 27%. Patients showed a tendency to compensate EHF score improvement before rft by worsening after rft and vice versa. The first main conclusion is that the impairment status at intake was by far the most important determinant for future impairment. The second one is that the dynamics of impairment were less favourable after rft than before. Little is known about the long-term fate of leprosy patients with irreversible nerve damage and the associated risk of developing severe secondary impairment. Especially in this era of the leprosy elimination goal, we should give this accumulating patient group due attention in research and health policy agendas.

The ALERT MDT Field Evaluation Study (AMFES): a descriptive study of leprosy in Ethiopia. Patients, methods and baseline characteristics.

The ALERT MDT Field Evaluation Study (AMFES) is a long-term prospective study of 650 patients (594 new cases and 56 relapses after dapsone monotherapy), treated with fixed-duration multiple-drug therapy (MDT), as recommended by WHO. Follow-up has continued for up to 11 years from the start of treatment. This paper presents the methodology of the study and the baseline characteristics of the cohort, while accompanying papers examine the incidence of, and possible risk factors for, the various complications of leprosy, including relapse, reactions and nerve function impairment. The methods of diagnosis, classification and treatment with MDT are described; nerve function was assessed at every visit to the clinic using a standardized methodology, so that reactions and new impairment could be detected early and treated. Eighty-four per cent of new case had at least one thickened nerve, with the ulnar nerve most commonly involved. Seventy-seven per cent of cases completed treatment and only one adverse reaction to the MDT drugs was noted. Twenty-eight per cent of all patients were given steroids at one time or another, almost always for new nerve function impairment, and 3% of these developed significant complications of steroid treatment. Twenty-nine patients (5%) received hospital care, including 14 patients who underwent major surgery. Sixty-one per cent of the women over 19 years of age had at least one pregnancy, but pregnancies were much less common after leprosy was diagnosed.

The pattern of leprosy-related neuropathy in the AMFES patients in Ethiopia: definitions, incidence, risk factors and outcome.

The ALERT MDT Field Evaluation Study (AMFES) began in 1988 and followed patients prospectively for up to 10 years after release from treatment (RFT). This paper presents the findings from this cohort with regard to neuropathy and nerve damage. Five hundred and ninety-four new cases of leprosy are included in the study, 300 multibacillary (MB) and 294 paucibacillary (PB) cases. Fifty-five percent of patients had some degree of impairment at diagnosis and a further 73 (12%) developed new nerve function impairment (NFI) after starting multiple drug therapy (MDT). The overall incidence rate for neuropathy was 39 episodes per 100 PYAR in the first year after diagnosis, gradually declining to 12 episodes per 100 PYAR in the sixth year. In those patients without impairment at diagnosis, the incidence rate of neuropathy was 25 episodes per 100 PYAR for MB cases and 11 per 100 PYAR for PB cases in the first year; in 33% of MB cases whose first episode of neuropathy occurred after diagnosis, that first episode took place after the first year, or after the normal period of treatment with MDT. Seventy-three patients with neuropathy developing after diagnosis are reported more fully: 34 (47%) had only one nerve involved and of these 25 (73%) had a single, acute episode of neuropathy. Nine (27%) had further episodes. Thirty-nine (53%) had more than one nerve involved and of these 16 (41%) had a single, acute episode, while 23 (59%) had further episodes. The terms 'chronic' and 'recurrent' neuropathy are defined and used to describe the pattern of neuropathy in those with repeated attacks. In patients with no impairment at the start of the study, treatment with steroids resulted in full recovery in 88% of nerves with acute neuropathy but only 51% of those with chronic or recurrent neuropathy. The median time to full recovery from acute neuropathy was approximately 6 months, but in a few cases recovery occurred gradually over 2-3 years. Severe neuropathy was less likely to be followed by a complete recovery than mild or moderate neuropathy. Forty-two percent of nerves with acute neuropathy that were not treated with steroids also fully recovered. In the group of patients who were thought to have old, permanent impairments at diagnosis, full recovery of nerve function occurred in 87/374 (23%) of the nerves involved. The overall outcome is illustrated by examining the average EHF score for groups of patients. Patients with no new neuropathy after diagnosis show a gradual improvement in their EHF score, while those with any episodes of neuropathy after diagnosis show a gradual deterioration after completion of MDT. Possible explanations for these findings are discussed. Risk factors for neuropathy, for chronic and recurrent neuropathy, and for a poor outcome 5 years after release from treatment, are examined. Impairment at diagnosis was the main risk factor for a poor outcome, accompanied by the occurrence of chronic/recurrent neuropathy or a reversal reaction.

The pattern of decline in bacillary index after 2 years of WHO recommended multiple drug therapy: the AMFES cohort.

With effective antibiotic treatment, the bacillary index (BI) in multibacillary leprosy patients declines over a number of years. This can be quantified as a rate of decline in log-units per year or as the time until smear negativity is reached. In the AMFES cohort 220 cases had data on the changes in their BI over time, while 170 cases are documented until smear negativity. The average BI at the start was 3.3 (SD 1.5; range 0.3-5.5) and the mean rate of decline was 0.85 units per year (median 0.7 units per year); in the first 2 years after diagnosis, the mean rate of decline was 1.15 units per year. The rate of decline was not related to any clinical features of the disease except delay in diagnosis: patients presenting for treatment early had a significantly faster rate of clearing the bacilli (adjusted relative risk 2.3; 95% CI 1.0-5.1). Fifty-eight percent of cases took longer than 3 years to reach smear negativity, but this time interval is largely determined by the initial BI and classification, making it a less useful indicator of bacterial clearance. More severe impairment at the start of treatment was associated with a faster return to smear negativity, for which no obvious explanation can be given. Reversal reactions, which occurred in 25% of the cases reviewed, are not associated with a more rapid clearance of bacilli.

Factors associated with impairments in new leprosy patients: the AMFES cohort.

Data on the importance of the delay between onset of symptoms and registration as a risk factor for impairment are sparse. This study investigates the quantitative relationship between this delay, other risk factors and the impairment status in new leprosy patients. It reports on 592 new leprosy patients enrolled in 1988-1992 in the prospective ALERT MDT Field Evaluation Study in central Ethiopia (AMFES). The influence of the risk factors sex, age, delay, PB/MB classification in relation to BI, and prior dapsone treatment on the impairment status at intake is analysed. Estimates for the delay are based on patient recall. For the risk factors, odds ratios on impairment and on severity of impairment were calculated using both univariate and multivariate logistic regression. The registration delay was 2 years or more for 44% of new patients. The prevalence of impairment (WHO impairment grades 1 and 2 combined) increased continuously from 36% for new patients with a delay of 0-1 year to 81% for new patients with delays of 4 years or more. This prevalence also increased continuously with age; it rose from 26% in children to 80% for the age group 60 and over. In the multivariate regression, the odds ratios for new patients to be impaired were statistically significant for all delay categories (baseline 1-2 years) and age groups (baseline 15-29 years). No statistically significant differences in odds ratios were observed with respect to sex and PB/MB classification in relation to BI. Overall, 31% of new patients presented with WHO impairment grade 1 and 23% with grade 2. The risk on grade 2 also increased with the registration delay amongst the impaired new patients. Relatively few impaired males and relatively few impaired MB patients with a BI value of 3 or higher had grade 2 impairment. Registration delay and age are the main risk factors for presentation with impairment. Reduction of delay in central Ethiopia requires re-thinking of control methodologies. The search for ways to reduce delays in diagnosis and treatment should receive high priority in leprosy research and in leprosy control programmes.

The lost muscles of the nose.

This is a review of the muscular anatomy of the nose. Areas of inconsistency in the main anatomy texts are highlighted and concentrate particularly on the omission of three identifiable muscles from modern textbooks. Two topographical areas of the nose in need of further anatomical development are identified. In a sample of 121 subjects from the general population, 40% were found to be incapable of flaring the nostrils voluntarily or subconsciously in conjunction with energetic inspiration with the mouth closed. The authors recommend systematic clinical assessment of the nasal musculature be incorporated in the pre- and postoperative examination of the rhinoplasty patient. The division of the nose into five sections for assessment is proposed and the muscles contributing to each area are defined together with their individual surgical relevance.

Non-Hodgkin's lymphoma presenting as median nerve compression in the arm.

A 70-year-old woman presented with median nerve compression secondary to enlarged supratrochlear lymph nodes infiltrated with malignant non-Hodgkin's lymphoma. Peripheral nerve compression is rarely seen in this condition. The management and prognosis are discussed.