Comparison of PCR with the routine procedure for diagnosis of tuberculosis in a population with high prevalences of tuberculosis and human immunodeficiency virus

Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) as employed in most low-income countries is cheap and easy to use, but its low sensitivity is a major drawback. The low specificity of chest X-rays, used for the diagnosis of smear-negative TB, risks high levels of overdiagnosis. Major advances in molecular techniques, which rapidly identify mycobacterial DNA in sputa, may overcome these obstacles. In this study, the AMPLICOR PCR system was used to diagnose pulmonary TB in a developing country with high prevalences of both TB and human immunodeficiency virus (HIV). The sensitivity and specificity of this technique were compared to those of the usual diagnostic techniques. Sputum specimens were collected from 1,396 TB suspects attending the Rhodes Chest Clinic, Nairobi, Kenya. The specimens were analyzed for the presence of Mycobacterium tuberculosis by PCR; culture on Löwenstein-Jensen medium was used as the “gold standard.” All culture-positive samples were genotyped to identify the mycobacterial species. The sensitivity and specificity of PCR were 93 and 84%, respectively. HIV status did not affect the sensitivity of PCR. A total of 99.7% of the true smear-positive and 82.1% of the true smear-negative TB patients were correctly identified by PCR. PCR detected M. tuberculosis in 11.7% of the culture-negative suspects, 60% of which had one or two PCR-positive sputum specimens. Of the 490 positive cultures, 486 were identified as M. tuberculosis. The high sensitivity of Amplicor PCR merits usage in a clinical setting with high TB and HIV burdens. Thus, PCR can be considered as an alternative to ZN staining in combination with chest X-ray for diagnosis of TB; however, cost-effectiveness studies and operational studies are required to support an evidence-based decision of introducing PCR for TB control in high-burden environments.Tuberculosis (TB) is one of the most serious infectious diseases and a considerable public health problem due to its high risk of person-to-person transmission, morbidity, and mortality. Both the human immunodeficiency virus (HIV) epidemic and social deterioration have contributed to the overall increase in the Mycobacterium tuberculosis infection rate, especially in developing countries, where resources are scarce (13). In Nairobi the case detection rate increased from 78 per 100,000 in 1991 to 581 per 100,000 in 2001, with a total number of 12,963 cases.Early diagnosis followed by adequate treatment is essential to prevent both morbidity and mortality. Although the conventional technique of direct smear examination with Ziehl-Neelsen staining (ZN) is cheap and easy to perform, its low sensitivity is a major drawback. Depending on the number of specimens examined, ZN detects 30 to 60% of the culture-positive “TB suspects” (7). Furthermore, it requires sputum samples collected on consecutive days, making the procedure slow and making patient compliance with the diagnostic process difficult.New techniques are very much needed (7), and molecular amplification assays such as PCR have been shown to be promising alternatives even for developing countries (2). PCR has the potential to be a cost-effective alternative, provided the diagnosis can be determined with one sputum examination (8). If diagnosis can be established faster, and the diagnostic process becomes less cumbersome for the patient, PCR may reduce delay both in diagnosis and in the start of treatment.Depending on the “gold standard” and other methodological factors, studies show PCR sensitivities ranging from 77% to more than 95% and PCR specificities of >95% for smear-positive specimens (4, 9, 10, 12). However, sensitivities for smear-negative TB patients have been reported to be below 90% (9). Most PCR studies have been performed in industrial countries (4, 9, 10, 12) where the TB and HIV burdens are low.To investigate the performance and feasibility of PCR in an environment of TB endemicity and high prevalences of HIV and AIDS, a study was conducted in Nairobi, Kenya, comparing PCR to conventional routine diagnostic methods within a program setup. In this study, the Roche Amplicor Mycobacteria PCR test for the direct detection of M. tuberculosis was used on sputum specimens from TB suspects attending a chest clinic in Nairobi. Its performance was compared with those of the basic routine diagnostic procedures according to the national guidelines (6), including clinical findings, ZN, and chest X-rays (CXR), on smear-negative suspects. Löwenstein-Jensen (LJ) culture results were used as the gold standard.     

Risk factors for pneumonia in urban-dwelling HIV-infected women: a case-control study in Nairobi,Kenya

In sub-Saharan Africa, respiratory tract infections (RTI) are the leading cause of serious morbidity and mortality in HIV-infected persons. This study sought to investigate demographic, socioeconomic, and environmental risk factors for pneumonia in a cohort of HIV-infected women. The authors performed a nested case-control study in a cohort of HIV-1-infected adults followed in Nairobi, Kenya. Thirty-nine women who developed pneumonia during the follow-up period were selected as cases, and 66 women who did not develop pneumonia were randomly chosen to serve as control subjects. A questionnaire was administered in subjects' homes that assessed demographics, home environment, and socioeconomic status. Women were followed in the cohort for a median of 36.8 months (range, 27.3-39.3). Adjusting for length of follow-up period, factors associated with lower socioeconomic status (lower monthly spending [OR = 3.2; 95% CI, 1.2-8.4 per 10,000 Kenyan shilling decrease], having no savings [OR = 4.1; 95% CI, 1.4-11.9], less sturdy home construction material such as mud or cement walls [OR = 2.6; 95% CI, 1.1-5.9] or dirt floors [OR = 2.8; 95% CI, 1.0-7.6], and lack of a window in the home [OR = 5.5; 95% CI, 0.9-32.2]) and being widowed (OR = 4.3; 95% CI, 1.2-15.1) or single (OR = 3.3; 95% CI, 1.0-11.2) were associated with an increased risk of pneumonia. In multivariate analysis, widowed (AOR = 5.9; 95% CI, 1.3-26.3), single (AOR = 7.7; 95% CI, 1.6-36.4), and divorced (AOR = 4.5; 95% CI, 1.0-20.1) women, those without savings (AOR = 3.7; 95% CI, 1.2-11.7), and those living in more crowded and contagious conditions (AOR = 1.5; 95% CI, 1.1-2.1) remained at increased risk of pneumonia. If confirmed by prospective investigation, these findings could help identify persons and subpopulations of HIV-infected women with the greatest risk of pneumonia.     

The economic burden of maternal mortality on households: evidence from three sub-counties in rural western Kenya

This study explores the consequences of a maternal death to households in rural Western Kenya focusing particularly on the immediate financial and economic impacts. Between September 2011 and March 2013 all households in the study area with a maternal death were surveyed. Data were collected on the demographic characteristics of the deceased woman; household socio-economic status; a history of the pregnancy and health care access and utilization; and disruption to household functioning due to the maternal death. These data were supplemented by in-depth and focus group discussions. The health service utilization costs associated with maternal deaths were significantly higher, due to more frequent service utilization as well as due to the higher cost of each visit suggesting more involved treatments and interventions were sought with these women. The already high costs incurred by cases during pregnancy were further increased during delivery and postpartum mainly a result of higher facility-based fees and expenses. Households who experienced a maternal death spent about one-third of their annual per capita consumption expenditure on healthcare access and use as opposed to at most 12% among households who had a health pregnancy and delivery. Funeral costs were often higher than the healthcare costs and altogether forced households to dis-save, liquidate assets and borrow money. What is more, the surviving members of the households had significant redistribution of labor and responsibilities to make up for the lost contributions of the deceased women. Kenya is in the process of instituting free maternity services in all public facilities. Effectively implemented, this policy can lift a major economic burden experienced by a very large number of household who seek maternal health services which can be catastrophic in complicated cases that result in maternal death. There needs to be further emphasis on insurance schemes that can support households through catastrophic health spending.     

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

Tigecycline (TIG) is approved for use for the treatment of complicated intra-abdominal infections, skin and skin structure infections, as well as pneumonia. Acquired resistance or reduced susceptibility to TIG has been observed in Gram-negative rods, has seldom been reported in Gram-positive organisms, and has not yet been reported in Enterococcus faecium. Using the serial passage method, in vitro mutant AusTig and in vitro mutants HMtig1 and HMtig2 with decreased TIG susceptibility (MICs, 0.25 μg/ml) were obtained from strains E. faecium Aus0004 and HM1070 (MICs, 0.03 μg/ml), respectively. In addition, two vancomycin-resistant E. faecium clinical isolates (EF16 and EF22) with reduced susceptibility to TIG (MICs, 0.5 and 0.25 μg/ml, respectively) were studied. Compared to the wild-type strains, the in vitro mutants also showed an increase in the MICs of other tetracyclines. An efflux mechanism did not seem to be involved in the reduced TIG susceptibility, since the presence of efflux pump inhibitors (reserpine or pantoprazole) did not affect the MICs of TIG. Whole-genome sequencing of AusTig was carried out, and genomic comparison with the Aus0004 genome was performed. Four modifications leading to an amino acid substitution were found. These mutations affected the rpsJ gene (efau004_00094, coding for the S10 protein of the 30S ribosomal subunit), efau004_01228 (encoding a cation transporter), efau004_01636 (coding for a hypothetical protein), and efau004_02455 (encoding the l-lactate oxidase). The four other strains exhibiting reduced TIG susceptibility were screened for the candidate mutations. This analysis revealed that three of them showed an amino acid substitution in the same region of the RpsJ protein. In this study, we characterized for the first time genetic determinants linked to reduced TIG susceptibility in enterococci.     

Clinical features and types of paediatric orofacial malignant neoplasms at two hospitals in Nairobi, Kenya

Aim

To evaluate the clinical features and histopathological types of orofacial malignant neoplasms in children.

Patients and methods

The study involved patients aged 15 years and below diagnosed with malignancy at two main referral hospitals in Kenya during the period from July, 2008 to December, 2008. A questionnaire and clinical examination chart were used to document data. Data analysis was done using SPSS 12.0 programme.

Results

65 children (44 males, 21 females) with ages ranging from 0.25 to 14 years were evaluated. The main complaints were swelling 61 (94%) and visual disturbance 29 (45%). The mean duration of symptoms was 0.17-36 months. The commonest signs were leucocoria (white reflection from the retina) 23 (35%), proptosis 19 (29%) and loss of vision 15 (23%). The commonest sites were orbit 30 (46%) and maxilla 11 (17%). Most neoplasms were retinoblastoma 26 (40%), followed by 14 (21%) cases of Burkitt’s lymphoma (BL) and occurred in patients under 5 years of age (40 cases) followed by 19 cases in children aged 5-10 years.

Conclusions

Overall, malignancies were more common in males than females with most having been diagnosed in children aged less than 10 years. Retinoblastoma and BL were the most common neoplasms.     

Effect of sustained insecticide-treated bed net use on all-cause child mortality in an area of intense perennial malaria transmission in western Kenya

We present results from a study conducted in western Kenya where all-cause child mortality was assessed among a population with high levels of sustained insecticide-treated bed net (ITN) use for up to six years. Although ITNs were associated with significant reductions in all-cause mortality among infants 1-11 months old, there was no difference in the rate of all-cause mortality among children 12-59 months old with ITNs for 2-4 years, compared historically with children from villages without ITNs, after controlling for seasonality and underlying child mortality across calendar years (adjusted hazard ratio [AHR] = 0.91, 95% confidence interval [CI] = 0.77-1.07). There was no increase in the proportion of child deaths at older ages (12-59 months old) of all child deaths within villages with ITNs for 5-6 years (48.1%) compared historically with villages without ITNs (47.9%), after controlling for seasonality (AHR = 1.03, P = 0.834). We find no evidence that sustained ITN use increased the risk of mortality in older children in this area of intense perennial malaria transmission.     

Prevalence of exercise induced bronchospasm in Kenyan school children: an urban-rural comparison

BACKGROUND: Higher rates of exercise induced bronchospasm (EIB) have been reported for urban than for rural African schoolchildren. The change from a traditional to a westernized lifestyle has been implicated. This study was undertaken to examine the impact of various features of urban living on the prevalence of EIB in Kenyan school children. METHODS: A total of 1226 children aged 8-17 years attending grade 4 at five randomly selected schools in Nairobi (urban) and five in Muranga district (rural) underwent an exercise challenge test. A respiratory health and home environment questionnaire was also administered to parents/guardians. This report is limited to 1071 children aged < or = 12 years. Prevalence rates of EIB for the two areas were compared and the differences analysed to model the respective contributions of personal characteristics, host and environmental factors implicated in childhood asthma. RESULTS: A fall in forced expiratory volume in one second (FEV1) after exercise of > or = 10% occurred in 22.9% of urban children and 13.2% of rural children (OR 1.96, 95% CI 1.41 to 2.71). The OR decreased to 1.65 (95% CI 1.10 to 2.47) after accounting for age, sex, and host factors (a family history of asthma and breast feeding for less than six months), and to 1.21 (95% CI 0.69 to 2.11) after further adjustment for environmental factors (parental education, use of biomass fuel and kerosene for cooking, and exposure to motor vehicle fumes). CONCLUSIONS: The EIB rates in this study are higher than any other reported for African children, even using more rigorous criteria for EIB. The study findings support a view which is gaining increasing credence that the increase in prevalence of childhood asthma associated with urbanisation is the consequence of various harmful environmental exposures acting on increasingly susceptible populations.     

Reproductive health issues in rural Western Kenya

Background  

We describe reproductive health issues among pregnant women in a rural area of Kenya with a high coverage of insecticide treated nets (ITNs) and high prevalence of HIV (15%).     

Use of intermittent preventive treatment for malaria in pregnancy in a rural area of western Kenya with high coverage of insecticide-treated bed nets

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through a cross-sectional, community-based survey in December 2002. Antenatal clinic (ANC) attendance was high (89.9% of the 635 participating women); 77.5% of attendees visited an ANC before the third trimester and 91.9% made more than one visit. Delivery of SP by the ANC was reported by 19.1% of all women but only 6.8% reported receiving more than one dose. Given the high rate of use of ANC services, if SP were given at each visit after the first trimester, the potential coverage of IPT (two doses of SP) would be 80.3% in this study population. ITNs were used by 82.4% of women during pregnancy, and almost all mothers (98.5%) who slept under an ITN shared the nets with their newborns after delivery. Women who thought malaria in pregnancy caused foetal problems were more likely to have used an ITN (adjusted odds ratio [AOR] 1.6, 95% confidence interval [CI] 1.0-2.4), and to have visited ANC more than once (AOR 2.4, 95% CI 1.2-4.7) compared to women who thought malaria in pregnancy was either not a problem or caused problems for the mother only. These findings illustrate the need for improved IPT coverage in this rural area. Identification and removal of the barriers to provision of IPT during ANC visits can help to increase coverage. In this area of Kenya, health messages stressing that foetal complications of malaria in pregnancy may occur in the absence of maternal illness may improve the demand for IPT.