The burden of disease caused by Streptococcus pneumoniae (pneumococcus) in young African children is well-established . A recent analysis estimated over 4 million cases and almost a half-million deaths from pneumococcal disease occur among African children < 5 years old annually . The burden of pneumococcal disease in older children and adults in Africa, particularly in rural settings, is less well-characterized, although is likely substantial. Several studies in Africa have shown pneumococcus to be one of the principal causes of severe bacterial bloodstream infections in hospitalized adults, along with Mycobacterium tuberculosis and non-typhi salmonellae .
The findings of a prevalence survey conducted in western Kenya, in a population with 14.9% HIV prevalence suggested inadequate case finding. We found a high burden of infectious and largely undiagnosed pulmonary tuberculosis (PTB), that a quarter of the prevalent cases had not yet sought care, and a low case detection rate.
The global burden of tuberculosis (TB) and HIV co-infections is immense. Of the 8.7 million incident cases of TB in 2011, an estimated 1.13 million (13%) were infected with HIV, of whom 430,000 (38%) died.  The highest rates of HIV co-infection were reported for TB patients in the African Region where 46% of those with a HIV test were HIV-positive. In some countries in the region, this figure was as high as 70%. . Africa is responsible for 79% of the HIV/TB infections globally. In Kenya, 106,000 cases of TB were registered in 2010 with 41% being HIV co-infected .
In Kenya there is need for proper co-ordination of antiretroviral therapy (ART) and tuberculosis (TB) treatment as most (60%) of the TB patients are also human immunodeficiency virus (HIV) positive. This study aims to determine the difference in response to TB treatment among HIV-negative TB patients and HIV-positive TB patients receiving delayed highly active antiretroviral therapy (HAART) at Vihiga District Hospital.
Scaling up the antiretroviral (ART) program in Kenya has involved a strategy of using clinical guidelines coupled with decentralization of treatment sites. However decentralization pushes clinical responsibility downwards to health facilities run by lower cadre staff. Whether the organizational culture in health facilities affects the outcomes despite the use of clinical guidelines has not been explored. This study aimed to demonstrate the relationship between organizational culture and early mortality and those lost to follow up (LTFU) among patients enrolled for HIV care.
KDH is located in Kericho among the tea fields and plantations of Kenya's southern Rift Valley Province 260 kilometers northwest of Nairobi. As a Ministry of Health (MoH) facility under the Ministry of Medical Services, KDH provides services to a rural, largely uninsured population, representative of the national statistic indicating that 46% of the population lives below the poverty line
Prevention of maternal-to-child transmission program at a tertiary care hospital in Nairobi, Kenya. The risk of acquiring Mycobacterium tuberculosis infection among peripartum human immunodeficiency virus (HIV) infected women is poorly defined.
To determine the incidence of and co-factors for interferon-gamma release assay (IGRA) conversion among postpartum HIV-infected women using T-SPOT.TB.
The tuberculin skin test (TST) can be used to identify HIV-infected people who would benefit the most from long-term isoniazid preventive therapy (IPT). However, in resource-constrained settings, implementation of the TST can be challenging. The objectives of this study were to assess the feasibility of implementing the TST for IPT initiation and to estimate the proportion of TST-positive incidence among HIV-positive patients in 2 high tuberculosis and HIV burden settings
Pulmonary aspergillomata usually develop in patients with underlying structural lung diseases. The mainstay of therapy is considered to be lung resection surgery - both for aspergillomata treatment and prevention of life-threatening haemoptysis
AIMS AND OBJECTIVES:
In the present study, we assessed the outcomes of patients with aspergillomata presented to a multi-disciplinary forum for resection and primarily assessed the proportion of patients who had surgery at the end of the follow-up period as well as the time duration to surgery.
The medical records of all patients diagnosed as having pulmonary aspergillomata and presented to a multidisciplinary forum for possible surgical resection at the Tygerberg Hospital, between January 2013 and December 2015, were retrospectively reviewed.
Fifty nine patients were included, with a mean (SD) age of 44.5 (± 8.8) years. Thirty six (61.0%) were male, and 13 (22.0%) were infected with human immunodeficiency virus (HIV). A previous history of pulmonary tuberculosis was identified in 83.1% of the patients. One or both upper lobes were involved in 58 of 59 patients (98.3%) and six patients (10.2%) had involvement of more than one lobe. Haemoptysis was the most frequent indication for surgery occurring in 56 patients (94.9%). Eleven patients (18.6%) reported ongoing respiratory symptoms within 90 days following discussion. After discussion, nine patients (15.3%) were considered unfit for surgery. Of those accepted, only 23 (46%) underwent surgical resection, as of 1 June 2016. The median time from presentation to surgery was 190 days (IQR: 134 – 351). Eighteen patients (78.3%) underwent resection of a single lobe, two (8.7%) had double lobectomies and three (13.0%) had pneumonectomies. There was no post-operative mortality. One patient developed bleeding, persistent air leak and aspiration pneumonia post- operatively requiring mechanical ventilation and an extended stay. Three further patients were hospitalised for >7 days, post-operatively. Fungal elements were identified in seventeen specimens (73.9%) of the resected lung. Following surgery, only two patient reported ongoing respiratory symptoms by day 90. Three of the 50 patients (6.0%) died prior to surgery from unknown causes. The reasons for delays and lack of surgery were varied and included: miscommunication (n=3); lack of transport (n=2); hospital bed shortage (n=1); refusal to consent (n=2); loss-to-follow-up (n=12); clinical improvement (n=3); clinical worsening (n=3) and lack of theatre space due to emergency procedures (n=1).
Lung resection surgery is considered the mainstay of therapy for pulmonary aspergillomata. However, in our institution, less than half of the patients accepted actually received surgery, waiting times were long (>1yr in 25%) and were associated with mortality. Barriers to prompt surgery are complex, but should be urgently addressed.
Universal access to ART has resulted in a reduction in HIV related morbidity and mortality. The increase in lifespan has however been accompanied by emergence of several Non-Communicable Diseases (NCDs). NCDs in HIV develop as a consequence of chronic inflammation, immunologic dysfunction, ART side effects, aging, and lifestyle factors. For purposes of this analysis, NCDs include diabetes mellitus (DM), hypertension, obesity, cardiovascular disease, and chronic kidney disease. NCD management is important to sustain gains made in controlling HIV infection and to prevent the double burden of disease in developing countries. This presents a challenge because the patients require close monitoring, have drug-drug interactions, suffer from pill burden and poor adherence. In addition, weaknesses in the health systems e.g. inadequate numbers of healthcare workers and capacity, lack of referral systems, poor access to laboratory tests and imaging, inadequate drugs, as well as lack of data, patient awareness and funding impedes the control NCDs.
Systems for screening and management of NCDs in HIV patients were set up . We reviewed patient charts for HIV infected patients with NCD followed up in 25 of these health facilities 3 years after setting up the systems. We analyzed for type of NCD, risk factors, services offered, and adherence using descriptive statistics.
A total of 416 patients with HIV and NCDs were assessed of which 75% had hypertension, 13% had diabetes, 6% were obese, 3% had heart diseases and 2% had chronic kidney disease. The mean age was 48.6 years and males accounted for 24.4% of these patients. Risk factors included smoking (8.6%), alcohol consumption (11.5%), BMI>25 (60.9%) and family history of DM, hypertension or heart disease (34%). Regarding service delivery systems for NCDs in the HIV clinic, 66.0% of the patients had coordinated appointments compared to none at baseline, 55.2% were referred for specialist review, and 74.0% received education related to NCD management compared to none at baseline. The types of messages given during education were promotion of physical activity given to 54.0% of the patients, dietary counseling to 76.1% of the patients and weight loss promotion given to 51.8% of the patients. ART adherence was assessed in 94.1% of the patients out of who 69.6% had good adherence, 4.0% had fair adherence, 2.6% had poor adherence and the remaining patients did not have their adherence level recorded. NCD medication adherence assessment was done in 88.9% of the patients out of who 60.0% had good adherence, 12.7% had fair adherence, 5.8% had poor adherence while the rest did not have their adherence levels recorded. In regard to routine clinical and laboratory monitoring, 93.3% had their BP recorded at every visit, 10.8% had annual lipid profile done, 25.1% had annual creatinine done, 27.2% received random blood sugar test, 5.9% had cardiovascular risk estimation done prior to treatment commencement and only 2.7% had GFR estimation done. Only 1% of the patients received all the monitoring services, 92.7% of the patients received some of the tests and 6.2% received none of these tests.
A lot has been invested in setting up chronic care models for the control of HIV. Lessons learnt here can form a foundation for setting up systems for integrated management of patients with both HIV and NCDs.
Traditional cardiovascular disease (CVD) risk factors contribute to increase risk of CVD in people living with HIV (PLWH). Of all world regions, sub-Saharan Africa has the highest prevalence of HIV yet little is known about PLWH’s CVD knowledge and self- perceived risk for coronary heart disease (CHD). In this study, we assessed PLWH’s knowledge, perception and attitude towards cardiovascular diseases and their prevention.
We conducted a cross-sectional study in the largest HIV care program in western Kenya. Trained research assistants used validated questionnaires to assess CVD risk patterns. We used logistic regression analysis to identify associations between knowledge with demographic variables, HIV disease characteristics, and individuals CVD risk patterns.
There were 300 participants in the study; median age (IQR) was 40 (33–46) years and 64% women. The prevalence of dyslipidemia, overweight and obesity were 70%, 33% and 8%, respectively. Participant’s knowledge of risk factors was low with a mean (SD) score of 1.3 (1.3) out of possible 10. Most (77.7%) could not identify any warning signs for heart attack. Higher education was a strong predictor of CVD risk knowledge (6.72, 95% CI 1.98-22.84, P<0.0001). Self-risk perception towards CHD was low (31%) and majority had inappropriate attitude towards CVD risk reduction.
Despite a high burden of cardiovascular risk factors, PLWH in Kenya lack CVD knowledge and do not perceived themselves at risk for CHD. These results emphasis the need for behavior changes interventions to address the stigma and promote positive health behaviors among the high risk HIV population in Kenya.
Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection.
Despite the evidence that isoniazid preventative therapy (IPT) reduces overall tuberculosis incidence, it is estimated that 5% of people living with HIV (PLHIV) have been screened for TB and 0.2% have been offered IPT. To improve TB case-finding, IPT initiation, and IPT completion among PLHIV in western Kenya, the Kenya TB Tech project was initiated. The first stage of TB Tech, reported here, describes processes and outcomes associated with using human-centered design techniques to develop a highly usable TB reminder system among pilot clinics. The second stage, a randomized clinical trial, assesses the clinical impacts of this reminders system.
With the aim of integrating HIV and tuberculosis care in rural Kenya, a team of researchers, clinicians, and technologists used the human-centered design approach to facilitate design, development, and deployment processes of new patient-specific TB clinical decision support system for medical providers. In Kenya, approximately 1.6 million people are living with HIV and have a 20-times higher risk of dying of tuberculosis. Although tuberculosis prevention and treatment medication is widely available, proven to save lives, and prioritized by the World Health Organization, ensuring that it reaches the most vulnerable communities remains challenging. Human-centered design, used in the fields of industrial design and information technology for decades, is an approach to improving the effectiveness and impact of innovations that has been scarcely used in the health field. Using this approach, our team followed a 3-step process, involving mixed methods assessment to (1) understand the situation through the collection and analysis of site observation sessions and key informant interviews; (2) develop a new clinical decision support system through iterative prototyping, end-user engagement, and usability testing; and, (3) implement and evaluate the system across 24 clinics in rural West Kenya. Through the application of this approach, we found that human-centered design facilitated the process of digital innovation in a complex and resource-constrained context.
During the period from 1980 to 1997, the annual number of new tuberculosis cases increased four-fold in Kenya, and had reached approximately 50 000 cases by 1998. During the same time period, the government per capita expenditure on health dropped from US$9.5 to US$3.5. Since 1983, Kenya has been decentralising financial responsibility and decision-making power to the districts. In addition, the late 1980s saw the introduction of cost-sharing schemes for most health services, excluding tuberculosis (TB) treatment. In the midst of these changes, a dual epidemic of TB and HIV/AIDS emerged, and is presently over-burdening the traditional public health system. In response, the National Leprosy and Tuberculosis Control Programme (NLTP) is seeking
a wider network of service providers and new approaches to the prevention and treatment of TB in the country. The history of health sector reform in Kenya is summarised and the role of the NLTP in these reforms assessed. Recent approaches taken by the NLTP to sustain effective TB control, which draw on the environment of a changing and flexible health system, are expressed. Participation of the NLTP in components of health sector reform, particularly decentralisation, integration, financing through cost-sharing and public/ private mix, are highlighted.
The purpose of this study is to evaluate the protective efficacy of two doses of GSK Biologicals' candidate TB vaccine against pulmonary TB, as compared to placebo. The efficacy will be evaluated in adults living in TB endemic countries and aged 18 - 50 years because pulmonary TB occurs frequently in these countries and age range. In addition, the safety and immunogenicity of the candidate tuberculosis vaccine will be evaluated in a subset of volunteers
The purpose of this study is to evaluate the impact of implementing a clinical decision support reminder system for medical providers (i.e., nurses, clinical officers, medical officers, consultants) to improve tuberculosis case-finding and the use of Isoniazid preventative therapy for adults living with HIV in western Kenya.
Multidrug-resistant (MDR) tuberculosis (TB) must be treated with second-line drugs (SLD) that are less effective, more toxic, and more expensive. Treatment requires at least 20 months with 4 or more effective drugs based on timely drug susceptibility test (DST) results. However, there are many examples of closely related drugs with differing antimicrobial activities.
Labs have found differences in DST results among the rifamycins, Rifampin (RMP) and Rifabutin (RBT); the fluoroquinolones, ofloxacin and Moxifloxacin; and the second-line injectable agents, kanamycin, amikacin, and Capreomycin. In a related finding, isolates resistant to 0.2 mcg/ml INH may be susceptible to higher concentrations. In the Preserving Effective Tuberculosis Treatment Study (PETTS), 32% of RMP-resistant isolates were susceptible to RBT, 41% of kanamycin-resistant isolates were susceptible to Capreomycin, and 45% of isolates resistant to 0.2 mcg/ml INH were susceptible to 1.0 or 5.0 mcg/ml (1). Other studies have demonstrated differences in DST results between Moxifloxacin and ofloxacin. Whether these in vitro results translate into clinical efficacy is completely unknown. Given the severely limited treatment options in MDR TB, it would be exceedingly useful to know whether these in vitro results translate into evidence for clinically meaningful treatment decisions.
The investigators will determine the clinical bactericidal activity of certain antibiotics against M. tab that appear to be effective in vitro even though closely related drugs from the same class are ineffective in vitro. Further, the investigators propose to determine the molecular genetic determinants of these differences.
Specifically, we plan to determine:
1. The bactericidal activity of RBT in patients whose baseline DST results demonstrate susceptibility to RBT and resistance to RMP.
2. The bactericidal activity of high-dose INH in patients whose baseline DST results demonstrate susceptibility to high concentrations of INH and resistance to low concentrations of INH.
3. The bactericidal activity of RMP when an approved molecular assay demonstrates genetic mutations associated with RMP resistance, but the phenotypic testing demonstrates susceptibility to RMP.
4. The bactericidal activity of Moxifloxacin in patients whose baseline DST results demonstrate susceptibility to Moxifloxacin and resistance to ofloxacin.
5. The bactericidal activity of amikacin and Capreomycin in patients whose baseline DST results demonstrate susceptibility to either of these two drugs and resistance to kanamycin.
6. The genetic mutations associated with both in vivo and in vitro drug resistance and bactericidal activity.
To achieve these objectives the investigators propose an innovative variation on early bactericidal activity (EBA) study methodology. Patients at risk for MDR TB will be screened for RMP resistance and INH resistance using molecular assays. In those with RMP-resistant or INH-resistant TB, the investigators will quickly perform phenotypic DSTs using the direct method in the BancTec Mycobacterium Growth Indicator Tube (MGIT) 960 system, so results will be available within 14-21 days. If the DST results show, for example, RMP resistance but susceptibility to RBT, consenting patients will be treated with RBT by itself for 10 days. The investigators will assess its effect with serial quantitative sputum cultures. If the concentration of viable bacteria decreases significantly, the investigators will interpret this to mean the drug is having an effect. If not, the drug is ineffective. After 10 days, the patients will resume individualized multidrug treatment based on the full set of DST results.
In case the investigators identify drugs that are effective under these conditions, the investigators will sequence known and putative genes associated with the action of these drugs for the mycobacterium isolates from these patients.
The results would have immediate implications for treatment of MDR TB and for diagnostic mycobacteriology.
HIV-infected people have an increased risk of developing active tuberculosis (TB). The standard course of treatment for TB is 6 to 9 months of Isoniazid (INH). A shorter course of treatment may be as effective and potentially increase treatment adherence. This study will compare the safety and effectiveness of a 4-week regimen of Rifapentine (RPT) plus INH versus a standard 9-month regimen of INH in HIV-infected people who are at risk of developing active TB.
Isoniazid preventive therapy (IPT) is a well studied clinical intervention for primary and secondary prevention of active tuberculosis (TB) after infection with Mycobacterium tuberculosis. It is widely used in industrialized countries in TB outbreak management, focusing on high risk groups such as close contacts in the family, in congregate settings, and in the workplace amongst others. Individuals infected with Human Immunodeficiency Virus (HIV) have a markedly higher risk of acquiring a TB-infection and developing consequently active TB, making HIV-infected individuals a target population for IPT. Studies of IPT in HIV infected persons in the nineties demonstrated the efficacy of IPT in the prevention of active TB in Sub -Saharan Africa and more recent studies suggest that the protective effect remains present in individuals on antiretroviral therapy.
Despite the proven efficacy of IPT this intervention has not been taken up by most HIV and TB control programmes in Africa where the burden of TB/HIV is highest. The reasons for the low uptake of IPT are many and varied but include fears of expansion of Isoniazid resistance and subsequently the development of multi -drug resistant TB with widespread use of IPT. Additionally screening protocols for excluding active TB and selecting persons for IPT have not been uniformly agreed upon. There have also been concerns that programmes designed to provide IPT may shift TB control programmes from their primary responsibility of finding and treating active TB. Finally it has been unclear as to which programme, between the HIV and the TB control programme, has the primary responsibility of managing the provision of the IPT intervention.
The World Health Organization and other technical agencies engaged in global TB control have recently re-emphasized the need to scale up IPT. In this proposal we outline an operational research study to evaluate the introduction of IPT at community level and to measure its effectiveness at preventing TB. The study is based on the context of expansion of Community-Based Direct Observed Therapy Short Course (CB-DOTS), home-based care and the concept of HIV prevention with positives (PwPs), where there is a real opportunity to focus on the household as a source of HIV-associated tuberculosis.
The study is designed as a cluster randomized trial. It compares the incidence of TB in household contacts including children under 5 of identified TB/HIV co-infected patients, who received IPT through proactive community intervention and those in a control group where the community was handled in the "usual way". In the intervention group household contacts of index cases of HIV positive, smear positive PTB will be visited at home and consenting contacts will be screened for active TB using a simple questionnaire. Those found to be fit will receive Isoniazid 300mg (5 mg per Kg for children) once daily for 6 months, regardless of the HIV-status. Those found not to be fit will be referred for further evaluation at the nearest TB diagnostic centre. In the control group, routine care following national guidelines will be offered. This consists of contact invitation and assessment of eligibility for IPT, especially, in children less than 5 years. Both groups will be followed up monthly through household visits. Follow up will be for a total of 24 months including the six months when IPT is provided.
A confidential HIV screening test will be provided to all consenting contacts in both intervention and control group after appropriate counseling.
The primary outcome is the incidence of TB in the intervention and control household contacts. The difference in incidence between the two groups is a measure of efficacy of the intervention. In addition the efficacy of the intervention will be estimated stratified by HIV status of household contacts if data allows. Secondary outcomes are the incidence of adverse events, the incidence of TB-related symptoms, measures on the uptake of IPT (proportion of contacts starting and discontinuing IPT, treatment adherence) and programmatic indicators, i.e. percentage of persons eligible for IPT and resources needed.