Risk Factors for Cervical Cancer in Ghana.

BACKGROUND: The major burden of cervical cancer occurs in low- and middle-income countries. In Ghana, it is the second most common cancer among women. Infection with high-risk human papilloma virus (HPV) has been established as the cause of cervical cancer. As such, it is important to identify risk factors that may affect progression from HPV infection to cancer. AIMS: We assessed the risk factors assocaited with cervical cancer in Ghana. METHODS: To identify the risk factors for cervical cancer, we conducted an unmatched case-control study in two hospitals in Ghana where most cervical cancer cases are diagnosed. Women with histologically confirmed cervical cancer were the cases, whereas women without cancer seeking care at the two hospitals were controls. A structured questionnaire was administered to the women, after which cervical samples were sent for HPV deoxyribonucleic acid (DNA) testing. RESULTS: Overall, 206 cases and 230 controls were recruited. After adjusting for possible confounders, women with the highest educational level had a significantly lower risk of cervical cancer than those with no or little formal education. Parity was a major risk factor (odd ratio [OR] for five or more children = 7.9; 95% CI: 2.3-27.6), with risk increasing with increasing parity (p for trend <0.001). Women reporting the use of a homemade sanitary towel during menstruation also had an increased risk of cervical cancer compared with women who used a pad (OR: 7.3; 95% CI: 2.5-22.0). CONCLUSION: In this Ghanaian population, high parity and poor personal hygienic conditions were the main contributing factors to the risk of cervical cancer after adjustment for the presence of high-risk HPV genotypes.

Selective under-representation of Pacific peoples in population estimates for health indicator measurements in Aotearoa New Zealand misinforms policy making.

BACKGROUND: The Census of Populations and Dwellings' is the five yearly population count of Aotearoa New Zealand. Best available populations (BAP) are subnational projections based on census data and demographic assumptions developed for healthcare planning and funding allocation but are also used as the denominator for health indicator monitoring. Pacific people are systematically undercounted, but the impact on health statistics is not well studied. For COVID-19 vaccination coverage, health service user (HSU) data were considered a more reliable denominator than BAP but introduced new biases. We aimed to understand how the choice of denominator population impacts estimates of population size and health system performance for Pacific people at a local level. METHODS: We described how declining census response rates affected population data quality. We compared BAP and HSU data at district level. For the indicators 'access to primary care' and 'cervical cancer screening uptake' we replaced currently used BAP denominators with HSU and examined the impact for different ethnic groups in different geographic districts. RESULTS: Overall Census 2018 response declined by 10%, but for Maori and Pacific people by 21% and 23%, respectively. This inequitably affected BAP accuracy. Census undercount was highest in the district with the largest Pacific populations, where HSU exceeded BAP most. Notably, 'access to primary care' for Pacific people in this district consistently exceeds 100%. Using BAP, both health indicators are currently estimated as highest for Pacific people compared to other ethnic groups, but when based on HSU, they dropped to lowest. Similar, but less pronounced trends occurred in other districts. Changes in trends over time for both indicators coincided mostly with adjustments in BAP, rather than changes in the numerators. CONCLUSIONS: The current use of BAP denominators for health statistics does not enable reliable monitoring of key health indicators for Pacific people. HSU denominators are also unsuitable for monitoring health. Exploring the feasibility of a real-time population register is strongly recommended as a new, transparent, way of obtaining more reliable, timely population data to guide policymaking and underpin a more equitable health system under the health reforms. Meanwhile, reporting of ethnic specific outcomes need to include a clear assessment of the potential for bias due to inaccurate population estimates.

Human papillomavirus genotype distribution among women with and without cervical cancer: Implication for vaccination and screening in Ghana.

INTRODUCTION: Determining the high-risk human papillomavirus (HR-HPV) genotypes burden in women with and without cervical cancer afford a direct comparison of their relative distributions. This quest is fundamental to implementing a future population-based cervical cancer prevention strategy in Ghana. We estimated the cervical cancer risk by HPV genotypes, and the HPV vaccine-preventable proportion of cervical cancer diagnosed in Ghana. MATERIALS AND METHODS: An unmatched case-control study was conducted at the two largest cervical cancer treatment centres in Ghana from 1st October 2014 to 31st May 2015. Cases were women diagnosed with cervical cancer and controls were women without cervical cancer who were seeking care at the two hospitals. Nested multiplex polymerase chain reaction (NM-PCR) was used to detect HPV infection in cervical samples. Logistic regression was used to determine the association between the risk of cervical cancer and identified HPV infection. P ≤0.05 was considered statistically significant. RESULTS: HPV deoxyribonucleic acid (DNA) data were analysed for 177 women with cervical cancer (cases) and 201 without cancer (controls). Cervical cancer was diagnosed at older ages compared to the age at which controls were recruited (median ages, 57 years vs 34 years; p < 0.001). Most women with cervical cancer were more likely to be single with no formal education, unemployed and less likely to live in metropolitan areas compared to women without cervical cancer (all p-value <0.001). HPV DNA was detected in more women with cervical cancer compared to those without cervical cancer (84.8% vs 45.8%). HR-HPV genotypes 16, 18, 45, 35 and 52 were the most common among women with cervical cancer, while 66, 52, 35, 43 and 31 were frequently detected in those without cancer. HPV 66 and 35 were the most dominant non-vaccine genotypes; HPV 66 was more prevalent among women with cervical cancer and HPV 35 in those without cervical cancer. Cervical cancer risk was associated with a positive HPV test (Adjusted OR (AOR): 5.78; 95% CI: 2.92-11.42), infection with any of the HR-HPV genotypes (AOR: 5.56; 95% CI: 3.27-13.16) or multiple HPV infections (AOR: 9.57 95% CI 4.06-22.56). CONCLUSION: Women with cervical cancer in Ghana have HPV infection with multiple genotypes, including some non-vaccine genotypes, with an estimated cervical cancer risk of about six- to ten-fold in the presence of a positive HPV test. HPV DNA tests and multivalent vaccine targeted at HPV 16, 18, 45 and 35 genotypes will be essential in Ghana's cervical cancer control programme. Large population-based studies are required in countries where cervical cancer is most prevalent to determine non-vaccine HPV genotypes which should be considered for the next-generation HPV vaccines.

Screening diabetes mellitus patients for pulmonary tuberculosis: a multisite study in Indonesia, Peru, Romania and South Africa.

BACKGROUND: Diabetes mellitus (DM) patients are three times more likely to develop tuberculosis (TB) than the general population. Active TB screening in people with DM is part of a bidirectional approach. The aim of this study was to conduct pragmatic active TB screening among DM patients in four countries to inform policy. METHODS: DM patients were recruited in Indonesia (n=809), Peru (n=600), Romania (n=603) and South Africa (n=51). TB cases were diagnosed using an algorithm including clinical symptoms and chest X-ray. Presumptive TB patients were examined with sputum smear and culture. RESULTS: A total of 171 (8.3%) individuals reported ever having had TB (South Africa, 26%; Indonesia, 12%; Peru, 7%; Romania, 4%), 15 of whom were already on TB treatment. Overall, 14 (0.73% [95% confidence interval 0.40 to 1.23]) TB cases were identified from screening. Poor glucose control, smoking, lower body mass index, education and socio-economic status were associated with newly diagnosed/current TB. Thirteen of the 14 TB cases diagnosed from this screening would have been found using a symptom-based approach. CONCLUSIONS: These data support the World Health Organization recommendation for routine symptom-based screening for TB in known DM patients in high TB-burden countries. DM patients with any symptoms consistent with TB should be investigated and diagnostic tools should be easily accessible.

Out-of-Pocket Costs for Patients Diagnosed with Tuberculosis in Different Healthcare Settings in Bandung, Indonesia.

Costs related to tuberculosis (TB) can impose a significant burden on patients and their families and create barriers to diagnosis and treatment. Our study aimed to quantify out-of-pocket costs expended by TB patients in Bandung, Indonesia. This cross-sectional study recruited adults with TB from community health centers (CHCs), public and private hospitals, and private practitioners (PPs). An interview was completed at the time of diagnosis or at their return for 2- or 6-month treatment. Costs were converted to U.S. dollars (US$)-presented as median and interquartile range (IQR). Of 469 TB patients recruited, the mean age was 38 years and 57% were male. The median pretreatment direct cost per person was $37.51 (IQR 20.79-71.24). Hospitalization, diagnostic tests, and travel costs were predominant. Higher pretreatment costs were associated with no health insurance ($41.88 versus $27.41, P < 0.001), ≥ 6 visits to a healthcare provider ($39.91 versus $24.32, P < 0.001), ≥ 60 days pretreatment ($36.35 versus $26.25, P = 0.02), and presenting first to a PP ($40.71) or informal provider ($32.72) compared with private hospital ($21.26), public hospital ($19.63), or CHC ($13.52) (P = 0.01). For a subsample of 106 patients with total pre- and posttreatment costs available, the median total cost was $243.66 (IQR 128.46-550.71). For 26.5% of these patients, total costs were ≥ 20% of their annual household income. Despite having a good network of free TB diagnostic and treatment services throughout Bandung, patients experienced significant out-of-pocket costs. Increased uptake of the National Health Insurance, and systems for early recognition and diagnosis of TB, will contribute toward reducing costs.

Towards elimination of tuberculosis in New Zealand.

New Zealand could be the first country in the world to eliminate tuberculosis (TB). We propose a TB elimination strategy based on the eight-point World Health Organization (WHO) action framework for low incidence countries. Priority actions recommended by the WHO include 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) identify active TB and undertake screening for latent tuberculosis infection (LTBI) in recent TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. In New Zealand, central government needs to take greater responsibility for TB policy and programme governance. Urgent action is required to prevent TB in higher risk groups including Maori communities, and to enable immigration screening to detect and treat LTBI. Clinical services need to be supported to implement new guidelines for LTBI that enable better targeting of screening and shorter, safer treatment regimens. Access to WHO recommended treatment regimens needs to be guaranteed for drug-resistant TB. Better use of existing data could better define priority areas for action and assist in the evaluation of current control activities. Access to GeneXpert® MTB-RIF near the point of care and whole genome sequencing nationally would greatly improve clinical and public health management through early identification of drug resistance and outbreaks. New Zealand already has a world-class TB research community that could be better deployed to assist high-incidence countries through research and training.

Accuracy of diabetes screening methods used for people with tuberculosis, Indonesia, Peru, Romania, South Africa.

OBJECTIVE: To evaluate the performance of diagnostic tools for diabetes mellitus, including laboratory methods and clinical risk scores, in newly-diagnosed pulmonary tuberculosis patients from four middle-income countries. METHODS: In a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen initial random plasma glucose was ≥ 6.1 mmol/L. FINDINGS: The overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6-14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75-0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81-0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru. CONCLUSION: Random plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemia, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation.

Disease characteristics and treatment of patients with diabetes mellitus attending government health services in Indonesia, Peru, Romania and South Africa.

OBJECTIVE: To describe the characteristics and management of Diabetes mellitus (DM) patients from low- and middle-income countries (LMIC). METHODS: We systematically characterised consecutive DM patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines. RESULTS: Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%) and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%) and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use. CONCLUSION: DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycaemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings.

Characteristics of Women Diagnosed with Invasive Cervical Cancer in Ghana

Objective: To describe the characteristics of women diagnosed with invasive cervical cancer from 2010 to 2013 in two large hospitals in Ghana. Method: Medical records and other hospital data on women diagnosed with invasive cervical cancer were collected from the Komfo Anokye and Korle-Bu Teaching Hospitals. Data were recorded onto a standardized data collection sheet and analyzed using summary statistics. Results: For of the 1,725 women with invasive cervical cancer who were included in the study, parity was high (5 and more births). The most common diagnostic investigation undertaken was a cervical biopsy, performed for 95.5% of cases. Few women had an imaging test performed as part of the diagnostic process (3.3%). Some had comorbid conditions at diagnosis (29.3%). Only 61% of women attended at least one follow-up appointment after diagnosis of their cancer. Conclusion: Our study suggests that more work is needed to improve patient education and access to diagnostic and treatment facilities to reduce the incidence and mortality of cervical cancer in Ghana. Additionally, improvement in data quality is needed to provide more complete data for cancer control in Ghana.

Cervical Cancer in the Greater Accra and Ashanti Regions of Ghana.

Purpose Cervical cancer is a common cancer among women worldwide. An estimated 528,000 new cases and 266,000 deaths occurred in 2012. More than 85% of invasive cervical cancer cases occur in low- and middle-income countries. Cervical cancer ranks as the most common cancer among women in Ghana. We conducted a retrospective study to assess the descriptive epidemiology of cervical cancer in Ghana. We describe cervical cancer incidence and mortality rates for the regions served by two large hospitals in Ghana. Patients and Methods Information for women diagnosed with invasive cervical cancer between 2010 and 2013 was collected from the Komfo Anokye and Korle Bu Teaching Hospitals through review of medical, computer, and pathology records at the oncology units and the obstetrics and gynecology departments. Telephone interviews were also conducted with patients and relatives. Data were analyzed using summary statistics. Results A total of 1,725 women with cervical cancer were included in the study. Their ages ranged from 11 to 100 years (mean, 56.9 years). The histology of the primary tumor was the basis of diagnosis in 77.5% of women and a clinical diagnosis was made in 22.5% of women. For the 1,336 women for whom tumor grade was available, 34.3% were moderately differentiated tumors. Late stage at presentation was common. The incidence and mortality rates of cervical cancer increased with age up until the 75 to 79-year age group and began to decrease at older ages. The Greater Accra region had higher overall incidence and mortality rates than the Ashanti region. Conclusion Our study suggests that improvements in the application of preventive strategies could considerably reduce the burden of cervical cancer in Ghana and other low- and middle-income countries. The study provides important information to inform policy on cancer prevention and control in Ghana.

Feasibility study of strengthening the public-private partnership for tuberculosis case detection in Bandung City, Indonesia.

OBJECTIVE: Private practitioner's (PPs) collaboration for detection, diagnosis and treatment of tuberculosis (TB) is recommended by the World Health Organization and encouraged by the Indonesian National TB control programme. TB case management by PPs, however, are mostly not in line with current guidelines. Therefore, we developed an intervention package for PPs comprising of TB training, implementation of a mobile phone application for notification of TB cases and a 6-month regular follow-up with PPs. This study aimed to evaluate the feasibility of the intervention package to increase TB case detection and notification rates among PPs in five community health centre areas in Bandung City, Indonesia. RESULTS: A total of 87 PPs were registered within the study area of whom 17 attended the training and 12 had the mobile phone application successfully installed. The remaining five PPs had phones that did not support the application. During the follow-up period, five PPs registered patients with TB symptoms and cases into the application. A total of 36 patients with TB symptoms were identified and 17 were confirmed TB positive.

Mycobacterium tuberculosis Infection in Close Childhood Contacts of Adults with Pulmonary Tuberculosis is Increased by Secondhand Exposure to Tobacco.

Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case. Contacts were tested with an enzyme-linked immunospot interferon gamma release assay. In multivariate regression models, M. tuberculosis infection was associated with increasing exposure to a case (odds ratios [OR]: 3.9, 95% confidence interval [CI]: 2.11-71.4, P < 0.001]) and with male gender (OR: 1.5 [95% CI: 1.12-2.11], P = 0.008). Tobacco use caused a 3-fold increase in the odds of M. tuberculosis infection in children who slept closest to a case who smoked within the same home compared with a nonsmoking case (OR: 8.0 [95% CI: 2.74-23.29] versus 2.4 [95% CI: 1.17-4.92], P < 0.001). SHS exposure as an effect modifier appears to greatly increase the risk of M. tuberculosis infection in children exposed to PTB cases. Smoking cessation campaigns may be important for reducing transmission of M. tuberculosis to children within households.

Factors Contributing to the Low Survival Among Women With a Diagnosis of Invasive Cervical Cancer in Ghana.

: Cervical cancer is one of the most common cancers among women worldwide, and more than 85% of the disease occurs in low- and middle-income countries. Although it ranks as the most common cancer in Ghanaian women, there are no data available on cervical cancer survival. METHODS: Information on women with a diagnosis of cervical cancer from 2010 to 2013 was collected from the Komfo Anokye and Korle-Bu Teaching Hospitals through review of paper-based and electronic medical records (including pathology records) at the oncology units and the departments of obstetrics and gynecology. Telephone interviews were conducted with patients and relatives to gather further information. Data were recorded using a standardized questionnaire and analyzed using summary statistics. RESULTS: Information for 821 women was available for the survival analysis. Of these, 497 (60.5%) died during follow-up. At 3 years after diagnosis, survival was 39%. Survival was lowest in women with stage IV disease. Women with squamous cell carcinoma had a survival advantage over those with adenocarcinoma. Furthermore, women who received surgery, radiotherapy, and chemotherapy had better survival than did women with other forms of treatment. CONCLUSIONS: In conclusion, cervical cancer survival is low in Ghana and is likely to be improved if a greater proportion of the disease is detected early. Improving knowledge of the disease for early diagnosis, reducing financial barriers, and greater organization of health care delivery are likely to improve survival from cervical cancer in Ghana.

No added value of interferon-γ release to a prediction model for childhood tuberculosis.

The predictive value of a combination of clinical and radiological features with interferon-γ release assay (IGRA) for diagnosis of active tuberculosis (TB) disease among TB-exposed children is unknown.150 symptomatic HIV-negative children (aged 3 months to 14 years), prospectively recruited through active contact tracing, were included. Backward stepwise logistic regression and bootstrapping techniques were used for the development and internal validation of a clinical prediction model for active TB disease. Model discrimination and incremental value of a positive IGRA test were assessed by area under the receiver operating characteristic curve (AUC).35 (23%) children were diagnosed with active TB disease and started on treatment and 115 (77%) had other respiratory tract infections. A final parsimonious clinical model, comprising age <5 years (adjusted (a)OR 4.8, 95% CI 2.0-11.5) and lymphadenopathy on clinical examination (aOR 4.9, 95% CI 1.8-13.0) discriminated active TB disease from other disease with an AUC of 0.70 (95% CI 0.61-0.80). A positive IGRA result did not improve the discriminatory ability of the clinical model (c-statistic 0.72 versus 0.70; p=0.644).A clinical algorithm, including age <5 years and lymphadenopathy classified 70% of active TB disease among symptomatic TB-exposed children. IGRA does not add any discriminatory value to this prediction model.

Prevalence of Chlamydia trachomatis infection in Samoan women aged 18 to 29 and assessment of possible risk factors: a community-based study.

BACKGROUND: Knowledge about genital Chlamydia trachomatis (CT) infections in the Pacific is limited. In this study we investigated CT infection in Samoan women. METHODS: We recruited women having unprotected sex aged 18 to 29 years from 41 Samoan villages. They completed a questionnaire and provided a urine sample for CT testing by PCR. Associations between CT infection and possible risk factors were explored using logistic regression. RESULTS: Altogether, 239 women were recruited; 86 (36.0%; weighted estimate of prevalence: 41.9%; 95% CI: 33.4-50.5%) were positive for CT infection. A higher proportion of women aged 18 to 24 were positive (54/145; 37.2%) than those aged 25 to 29 (32/94; 34.0%; p=0.20). Being single (OR 1.92; 95% CI: 1.02-3.63) and having two or more lifetime sexual partners (OR 3.02; 95% CI: 1.19-7.67) were associated with CT infection; 27.6% of those with one lifetime partner were positive. Participants who had a previous pregnancy were less likely to be positive (OR 0.49; 95% CI: 0.27-0.87). Primiparous and multiparous women were less likely to be positive than nulliparous women (OR 0.54; 95% CI: 0.30-0.99 and OR 0.46; 95% CI: 0.24-0.89, respectively). CONCLUSIONS: The prevalence of CT infection in these Samoan women is very high. Further studies, including investigating the prevalence of CT infection in men, and strategies for sustainable control are needed.

Clinical management of concurrent diabetes and tuberculosis and the implications for patient services.

Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management of patients with both diseases can be difficult. Tuberculosis patients with diabetes have a lower concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes. Good glycaemic control, which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors. Besides drug treatments for tuberculosis and diabetes, other interventions, such as education, intensive monitoring, and lifestyle interventions, might be needed, especially for patients with newly diagnosed diabetes or those who need insulin. From a health systems point of view, delivery of optimum care and integration of services for tuberculosis and diabetes is a huge challenge in many countries. Experience from the combined tuberculosis and HIV/AIDS epidemic could serve as an example, but more studies are needed that include economic assessments of recommended screening and systems to manage concurrent tuberculosis and diabetes.

Management of children exposed to Mycobacterium tuberculosis: a public health evaluation in West Java, Indonesia.

OBJECTIVE: To investigate qualitatively and quantitatively the performance of a programme for managing the child contacts of adult tuberculosis patients in Indonesia. METHODS: A public health evaluation framework was used to assess gaps in a child contact management programme at a lung clinic. Targets for programme performance indicators were derived from established programme indicator targets, the scientific literature and expert opinion. Compliance with tuberculosis screening, the initiation of isoniazid preventive therapy in children younger than 5 years, the accuracy of tuberculosis diagnosis and adherence to preventive therapy were assessed in 755 child contacts in two cohorts. In addition, 22 primary caregivers and 34 clinic staff were interviewed to evaluate knowledge and acceptance of child contact management. The cost to caregivers was recorded. Gaps between observed and target indicator values were quantified. FINDINGS: THE GAPS BETWEEN OBSERVED AND TARGET PERFORMANCE INDICATORS WERE: 82% for screening compliance; 64 to 100% for diagnostic accuracy, 50% for the initiation of preventive therapy, 54% for adherence to therapy and 50% for costs. Many staff did not have adequate knowledge of, or an appropriate attitude towards, child contact management, especially regarding isoniazid preventive therapy. Caregivers had good knowledge of screening but not of preventive therapy and had difficulty travelling to the clinic and paying costs. CONCLUSION: The study identified widespread gaps in the performance of a child contact management system in Indonesia, all of which appear amenable to intervention. The public health evaluation framework used could be applied in other settings where child contact management is failing.

Genetic variants of MARCO are associated with susceptibility to pulmonary tuberculosis in a Gambian population.

BACKGROUND: The two major class A scavenger receptors are scavenger receptor A (SRA), which is constitutively expressed on most macrophage populations, and macrophage receptor with collagenous structure (MARCO), which is constitutively expressed on a more restricted subset of macrophages, (e.g. alveolar macrophages) but whose expression increases on most macrophages during the course of infection. Although the primary role of SRA appears to be clearance of modified host proteins and lipids, mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection and in vitro assays, the scavenger receptors have been demonstrated to bind bacteria and to enhance pro-inflammatory signalling to many bacterial lung pathogens; however their importance in Mycobacterium tuberculosis infection, is less clear. METHODS: To determine whether polymorphisms in either SRA or MARCO were associated with tuberculosis, a case-control study of was performed. DNA samples from newly-detected, smear-positive, pulmonary tuberculosis cases were collected from The Gambia. Controls for this study consisted of DNA from cord bloods obtained from routine births at local Gambian health clinics. Informed written consent was obtained from patients or their parents or guardians. Ethical approval was provided by the joint The Gambian Government/MRC Joint Ethics Committee. RESULTS: We studied the frequencies of 25 polymorphisms of MSR1 (SRA) and 22 in MARCO in individuals with tuberculosis (n=1284) and matched controls (n=1349). No SNPs within the gene encoding or within 1 kb of the promoter sequence of MSR1 were associated with either susceptibility or resistance to tuberculosis. Three SNPs in MARCO (rs4491733, Mantel-Haenszel 2x2 χ2 = 6.5, p = 0.001, rs12998782, Mantel-Haenszel 2x2 χ2 = 6.59, p = 0.001, rs13389814 Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) were associated with susceptibility to tuberculosis and one (rs7559955, Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) was associated with resistance to tuberculosis. CONCLUSIONS: These findings identify MARCO as a potentially important receptor in the host response to tuberculosis.

Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions.

Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers. These barriers are largely resolvable, and proposed solutions such as the adoption of symptom-based screening and shorter drug regimens are discussed. Integrated multicomponent and site-specific solutions need to be developed and evaluated within a public health framework to overcome the policy-practice gap and provide functional PT programmes for children in endemic settings.