Delay in Tuberculosis Case-Finding and Treatment in Mwanza, Tanzania.

Health facilities in Mwanza region, Tanzania. To determine factors responsible for delay from onset of symptoms of pulmonary tuberculosis to initiation of treatment. A cross-sectional descriptive study of 296 smear-positive tuberculosis patients. Emphasis was given to periods between 1) onset of symptoms and first consultation to a health facility, and 2) reporting to a health facility and initiation of treatment. Mean total delay was 185 days (median 136), with nearly 90% of this being patient's delay. The mean health system delay was 23 days (median 15), with longer delays in rural health facilities. The mean patient's delay was 162 days (median 120). This delay was significantly longer in rural areas, for patients with lower level of education, for those who first visited a traditional healer, and for patients who had no information on tuberculosis prior to diagnosis. Only 15% of the patients reported to a health facility within 30 days of onset of symptoms. There are significant delays in case-finding in Mwanza, Tanzania, with prolonged patient's delay. Facilitation of utilisation of health services, raising awareness of the disease and incorporation of private practice into tuberculosis control could help to reduce these delays.\u

Gender differences in the clinical diagnosis of tuberculous lymphadenitis—a hospital-based study from Central India

SummaryObjectiveTuberculous lymphadenitis can be difficult to diagnose clinically, and as it is thought to be more common in females, we describe here the clinical characteristics of cervical tuberculous lymphadenitis in men and women and compare this with cytology to assess their diagnostic value.MethodsTwo hundred and nineteen patients with tuberculous lymphadenitis, aged 14 years or more, who presented with a neck mass to the Department of Pathology, Ujjain Hospital, Ujjain, India were included in the study. The presenting clinical symptoms and signs were compared between men and women and with the cytology of fine needle aspirates from the lymph nodes.ResultsSeventy-five percent of the patients were aged between 14 and 35 years, with a male to female ratio of 1:2.1. One or more constitutional symptoms were present in 56.6% of patients on presentation. There were more men with clinical symptoms than women. Fever was the most common manifestation in both gender groups. Fever for more than 30 days, cough, weight loss, and night sweats were significantly more common in men. On cytology, necrotic granulomas were found to be associated with constitutional symptoms.ConclusionsConstitutional symptoms were more frequently reported by men than by women and showed a correlation with necrotic granulomas on cytology

A qualitative case study of community experiences with Tungiasis in high prevalence villages of Bungoma County, Kenya: “The whole body aches and the jiggers are torturing me!”

Introduction: Tungiasis is a painful skin infection caused by a flea called Tunga Penetrans/jiggers, which enters the epidermis of humans and animals. If untreated it may result in bacterial infection, sepsis, necrosis, and disability. In Kenya, it is estimated that 4% of the population suffer from jigger infestation. The aim of this study was to contribute with knowledge about the experiences of those affected, perceived causes and local coping strategies, to improve the control and elimination of this neglected condition. Method: A qualitative case study research design was applied involving fieldwork in Bungoma County, a high-prevalence rural area in Western Kenya. Multiple data collection methods were combined: participant observation, home visits, semi- structured in-depth interviews, and group discussions. In total, 48 informants participated, including infected children and adults, teachers and pupils, public health officers, community health workers and NGO volunteers. Results: Those infected suffered with multiple penetrating wounds on hands and feet that cause disability, resulting in an incapacity to work and school drop-out. People described feeling stigmatized, and at school pupils preferred not to play with infected classmates. People perceived that the sand flea infestation was caused by poverty and that those affected were not even able to cover their basic needs. They were often living in sandy huts that they shared with their animals, without access to soap and clean water. Moreover, those infected were often viewed as ignorant by the rest of the community. Informants perceived recurrence after treatment as inevitable, resulting in creation of hopelessness. Those infected felt that they were left alone with an irremediable plague. There was confusion about effective approaches regarding prevention and treatment at all levels. Conclusion: Tungiasis is a debilitating and neglected ailment, inflicting severe suffering and increasing the circle of poverty. To address fatalist attitudes among those affected, national guidelines need to be implemented, and coordination of public health measures regarding prevention and treatment need to be strengthened. Further research is recommended to enable the control and elimination of this neglected tropical diseasepublishedVersio

Immunohistochemical diagnosis of abdominal and lymph node tuberculosis by detecting Mycobacterium tuberculosis complex specific antigen MPT64

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the diagnostic potential of immunohistochemistry using an antibody to the secreted mycobacterial antigen MPT64, in abdominal and lymph node tuberculosis.</p> <p>Methods</p> <p>We used formalin-fixed histologically diagnosed abdominal tuberculosis (n = 33) and cervical tuberculous lymphadenitis (n = 120) biopsies. These were investigated using a combination of Ziehl-Neelsen method, culture, immunohistochemistry with an antibody to MPT64, a specific antigen for <it>Mycobacterium tuberculosis</it> complex organisms. Abdominal and cervical lymph node biopsies from non-mycobacterial diseases (n = 50) were similarly tested as negative controls. Immunohistochemistry with commercially available anti-BCG and nested PCR for IS6110 were done for comparison. Nested PCR was positive in 86.3% cases and the results of all the tests were compared using nested PCR as the gold standard.</p> <p>Results</p> <p>In lymph node biopsies, immunohistochemistry with anti-MPT64 was positive in 96 (80%) cases and 4 (12.5%) controls and with anti-BCG 92 (76.6%), and 9 (28%) respectively. The results for cases and controls in abdominal biopsies were 25 (75.7%) and 2 (11.1%) for anti-MPT64 and 25 (75.7%) and 4 (22%) for anti-BCG. The overall sensitivity, specificity, positive and negative predictive values of immunohistochemistry with anti-MPT64 was 92%, 97%, 98%, and 85%, respectively while the corresponding values for anti-BCG were 88%, 85%, 92%, and 78%.</p> <p>Conclusion</p> <p>Immunohistochemistry using anti-MPT64 is a simple and sensitive technique for establishing an early and specific diagnosis of <it>M. tuberculosis</it> infection and one that can easily be incorporated into routine histopathology laboratories.</p

Transgenerational and intergenerational epigenetic inheritance in allergic diseases

It has become clear that early life (including in utero exposures) is a key window of vulnerability during which environmental exposures can alter developmental trajectories and initiate allergic disease development. However, recent evidence suggests that there might be additional windows of vulnerability to environmental exposures in the parental generation before conception or even in previous generations. There is evidence suggesting that information of prior exposures can be transferred across generations, and experimental animal models suggest that such transmission can be conveyed through epigenetic mechanisms. Although the molecular mechanisms of intergenerational and transgenerationational epigenetic transmission have yet to be determined, the realization that environment before conception can alter the risks of allergic diseases has profound implications for the development of public health interventions to prevent disease. Future research in both experimental models and in multigenerational human cohorts is needed to better understand the role of intergenerational and transgenerational effects in patients with asthma and allergic disease. This will provide the knowledge basis for a new approach to efficient intervention strategies aimed at reducing the major public health challenge of these conditions.publishedVersio

Low Immunization Rate in Kidney Transplant Recipients Also After Dose 2 of the BNT162b2 Vaccine: Continue to Keep Your Guard up!

publishedVersio

Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study

Epidemiological studies suggest that father’s smoking might influence their future children’s health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers’ smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11–54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006–0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR)  < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers’ smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers’ exposures might persistently modify their future offspring’s epigenome.publishedVersio

Smear microscopy and culture conversion rates among smear positive pulmonary tuberculosis patients by HIV status in Dar es Salaam, Tanzania

Tanzania ranks 15th among the world's 22 countries with the largest tuberculosis burden and tuberculosis has continued to be among the major public health problems in the country. Limited data, especially in patients co infected with HIV, are available to predict the duration of time required for a smear positive pulmonary tuberculosis patient to achieve sputum conversion after starting effective treatment. In this study we assessed the sputum smear and culture conversion rates among HIV positive and HIV negative smear positive pulmonary tuberculosis patients in Dar es Salaam The study was a prospective cohort study which lasted for nine months, from April to December 2008 A total of 502 smear positive pulmonary tuberculosis patients were recruited. HIV test results were obtained for 498 patients, of which 33.7% were HIV positive. After two weeks of treatment the conversion rate by standard sputum microscopy was higher in HIV positive(72.8%) than HIV negative(63.3%) patients by univariate analysis(P = 0.046), but not in multivariate analysis. Also after two weeks of treatment the conversion rate by fluorescence microscopy was higher in HIV positive (72.8%) than in HIV negative(63.2%) patients by univariate analysis (P = 0.043) but not in the multivariate analysis. The conversion rates by both methods during the rest of the treatment period (8, 12, and 20 weeks) were not significantly different between HIV positive and HIV negative patients.With regards to culture, the conversion rate during the whole period of the treatment (2, 8, 12 and 20 weeks) were not significantly different between HIV positive and HIV negative patients.\ud Conversion rates of standard smear microscopy, fluorescence microscopy and culture did not differ between HIV positive and HIV negative pulmonary tuberculosis patients

Genetic profile of Mycobacterium tuberculosis and treatment outcomes in human pulmonary tuberculosis in Tanzania

Information on the different spoligotype families of Mycobacterium tuberculosis in Tanzania is limited, and where available is restricted to small geographical areas.  This article describes the genetic profile of M. tuberculosis across Tanzania and suggests how spoligotype families might affect drug resistance and treatment outcomes for smear positive pulmonary tuberculosis patients in Tanzania. In this study conducted from 2006 to 2008, the M. tuberculosis isolates were obtained from samples collected under the routine drug resistance surveillance system. The isolates were from specimens collected from 2001 to 2007, and stored at the Central and Reference Tuberculosis Laboratory in Dar es Salaam. A total of 487 isolates from 23 regions in Tanzania were spoligotyped. However, clinical information for 446 isolates was available. Out of the 487 isolates spoligotyped, 195 (40.0%) belonged to the Central Asian (CAS) family, 84 (17.5%) to the Latin American Mediterranean (LAM) family, 49 (10.1%) to the East-African Indian (EAI) family, and 33 (6.8%) to the Beijing family. Other isolates included 1 (0.2%) for H37Rv, 10 (2.1%) for Haarlem, 4 (0.8%) for S family, 58 (11.9%) for T family and 52 (10.7%) for unclassified.  No spoligotype patterns were consistent with M. bovis. As regards to treatment outcomes, the cure rate was 80% with no significant variation between the spoligotype families.  The overall level of MDR-TB was 2.5% (3/121), with no significant difference between the spoligotype families. All Beijing strains (11.8%, 30/254) originated from the Eastern and Southern zones of the country, of which 80% were from Dar es Salaam.  Isolates from the CAS and T families were reported disproportionately from the Eastern-Southern zone, and EAI and LAM families from the Northern-Lake zones but the difference was not statistically significant. Five isolates were identified as Non-tuberculous Mycobacteria. In conclusion, M. tuberculosis isolates from pulmonary tuberculosis cases in Tanzania were classified mostly within the CAS, LAM, and EAI and T families.  Consistently good treatment outcomes were recorded across the spoligotype families.  The proportion of drug resistance strains was low. The findings also suggest variation of spoligotype families with varying geographical localities within the country. 

Current status of medication adherence and infant follow up in the prevention of mother to child HIV transmission programme in Addis Ababa: a cohort study

<p>Abstract</p> <p>Background</p> <p>Prevention of mother to child HIV transmission (PMTCT) programmes have great potential to achieve virtual elimination of perinatal HIV transmission provided that PMTCT recommendations are properly followed. This study assessed mothers and infants adherence to medication regimen for PMTCT and the proportions of exposed infants who were followed up in the PMTCT programme.</p> <p>Methods</p> <p>A prospective cohort study was conducted among 282 HIV-positive mothers attending 15 health facilities in Addis Ababa, Ethiopia. Descriptive statistics, bivariate and mulitivariate logistic regression analyses were done.</p> <p>Results</p> <p>Of 282 mothers enrolled in the cohort, 232 (82%, 95% CI 77-86%) initiated medication during pregnancy, 154 (64%) initiated combined zidovudine (ZDV) prophylaxis regimen while 78 (33%) were initiated lifelong antiretroviral treatment (ART). In total, 171 (60%, 95% CI 55-66%) mothers ingested medication during labour. Of the 221 live born infants (including two sets of twins), 191 (87%, 95% CI 81-90%) ingested ZDV and single-dose nevirapine (sdNVP) at birth. Of the 219 live births (twin births were counted once), 148 (68%, 95% CI 61-73%) mother-infant pairs ingested their medication at birth. Medication ingested by mother-infant pairs at birth was significantly and independently associated with place of delivery. Mother-infant pairs attended in health facilities at birth were more likely (OR 6.7 95% CI 2.90-21.65) to ingest their medication than those who were attended at home. Overall, 189 (86%, 95% CI 80-90%) infants were brought for first pentavalent vaccine and 115 (52%, 95% CI 45-58%) for early infant diagnosis at six-weeks postpartum. Among the infants brought for early diagnosis, 71 (32%, 95% CI 26-39%) had documented HIV test results and six (8.4%) were HIV positive.</p> <p>Conclusions</p> <p>We found a progressive decline in medication adherence across the perinatal period. There is a big gap between mediation initiated during pregnancy and actually ingested by the mother-infant pairs at birth. Follow up for HIV-exposed infants seem not to be organized and is inconsistent. In order to maximize effectiveness of the PMTCT programme, the rate of institutional delivery should be increased, the quality of obstetric services should be improved and missed opportunities to exposed infant follow up should be minimized.</p