Financial barriers and coping strategies: a qualitative study of accessing multidrug-resistant tuberculosis and tuberculosis care in Yunnan, China.

BACKGROUND: Tuberculosis (TB) and multidrug-resistance tuberculosis (MDR-TB) pose serious challenges to global health, particularly in China, which has the second highest case burden in the world. Disparities in access to care for the poorest, rural TB patients may be exacerbated for MDR-TB patients, although this has not been investigated widely. We examine whether certain patient groups experience different barriers to accessing TB services, whether there are added challenges for patients with MDR-TB, and how patients and health providers cope in Yunnan, a mountainous province in China with a largely rural population and high TB burden. METHODS: Using a qualitative study design, we conducted five focus group discussions and 47 in-depth interviews with purposively sampled TB and MDR-TB patients and healthcare providers in Mandarin, between August 2014 and May 2015. Field-notes and interview transcripts were analysed via a combination of open and thematic coding. RESULTS: Patients and healthcare providers consistently cited financial constraints as the most common barriers to accessing care. Rural residents, farmers and ethnic minorities were the most vulnerable to these barriers, and patients with MDR-TB reported a higher financial burden owing to the centralisation and longer duration of treatment. Support in the form of free or subsidised treatment and medical insurance, was deemed essential but inadequate for alleviating financial barriers to patients. Most patients coped by selling their assets or borrowing money from family members, which often strained relationships. Notably, some healthcare providers themselves reported making financial and other contributions to assist patients, but recognised these practices as unsustainable. CONCLUSIONS: Financial constraints were identified by TB and MDR-TB patients and health care professionals as the most pervasive barrier to care. Barriers appeared to be magnified for ethnic minorities and patients coming from rural areas, especially those with MDR-TB. To reduce financial barriers and improve treatment outcomes, there is a need for further research into the total costs of seeking and accessing TB and MDR-TB care. This will enable better assessment and targeting of appropriate financial support for identified vulnerable groups and geographic development of relevant services.

Are current case-finding methods under-diagnosing tuberculosis among women in Myanmar? An analysis of operational data from Yangon and the nationwide prevalence survey.

BACKGROUND: Although there is a large increase in investment for tuberculosis control in Myanmar, there are few operational analyses to inform policies. Only 34% of nationally reported cases are from women. In this study, we investigate sex differences in tuberculosis diagnoses in Myanmar in order to identify potential health systems barriers that may be driving lower tuberculosis case finding among women. METHODS: From October 2014 to March 2015, we systematically collected data on all new adult smear positive tuberculosis cases in ten township health centres across Yangon, the largest city in Myanmar, to produce an electronic tuberculosis database. We conducted a descriptive cross-sectional analysis of sex differences in tuberculosis diagnoses at the township health centres. We also analysed national prevalence survey data to calculate additional case finding in men and women by using sputum culture when smear microscopy was negative, and estimated the sex-specific impact of using a more sensitive diagnostic tool at township health centres. RESULTS: Overall, only 514 (30%) out of 1371 new smear positive tuberculosis patients diagnosed at the township health centres were female. The proportion of female patients varied by township (from 21% to 37%, p = 0.0172), month of diagnosis (37% in February 2015 and 23% in March 2015 p = 0.0004) and age group (26% in 25-64 years and 49% in 18-25 years, p < 0.0001). Smear microscopy grading of sputum specimens was not substantially different between sexes. The prevalence survey analysis indicated that the use of a more sensitive diagnostic tool could result in the proportion of females diagnosed at township health centres increasing to 36% from 30%. CONCLUSIONS: Our study, which is the first to systematically compile and analyse routine operational data from tuberculosis diagnostic centres in Myanmar, found that substantially fewer women than men were diagnosed in all study townships. The sex ratio of newly diagnosed cases varied by age group, month of diagnosis and township of diagnosis. Low sensitivity of tuberculosis diagnosis may lead to a potential under-diagnosis of tuberculosis among women.

Late diagnosis of HIV in Europe: definitional and public health challenges.

With universal access to antiretroviral therapy (ART), people can access effective treatment but are only able to benefit from these advances if they are aware of their status and are effectively accessing testing services. Although it was anticipated in the mid-1990s that the availability of ART would lead to earlier testing, this trend has not been observed in practice, with stagnant or even increasing rates of late diagnosis in Europe. Ahead of a gathering of key European stakeholders in Brussels in November 2007, we reviewed definitions of late diagnosis and approaches to surveillance of late HIV diagnosis in Europe. We found that there is no common or consistent reporting of late diagnosis across Europe and that the multiplicity of definitions for late diagnosis is likely proving a hindrance to providing information on the magnitude of the problem, determining trends, and informing understanding of reasons for changes in trends. We also show that existing evidence points to high rates of late diagnosis across Europe - between 15 and 38% of all HIV cases - and concur that trends that are increasing or at best stagnant. We identify risk factors that are associated with individuals being more likely to present late and we explore the reasons for late presentation. We reflect on the need to review surveillance and testing policies, notably in relation for population groups that are heavily represented in late presenters and make recommendations for a coherent, cross-European approach to surveillance and monitoring in order to support improvements in service provision and, ultimately, public health.

HIV testing strategies across European countries.

With universal access to effective combination antiretroviral therapy (ART), people in need can gain effective treatment but are only able to benefit from these advances if they are aware of their serostatus and have effectively accessed testing services. Despite the expectation that ART would lead individuals to seek earlier testing, this trend has not been observed in practice, with stable or even increasing rates of late diagnosis in Europe being witnessed. Ahead of a gathering of key European stakeholders in Brussels in November 2007, we reviewed testing strategies across European countries. We show differences in policy and practices. Moreover, HIV testing strategies are changing, in line with new global guidelines issued by World Health Organization headquarters, and a number of countries are promoting an expansion of routine and opt-out testing. However, gaps in our understanding of effective testing strategies remain and, as a consequence, national policies across Europe remain incoherent and often lack an evidence base. This is likely to have serious public health implications.

Are global tuberculosis control targets overlooking an essential indicator? Prolonged delays to diagnosis despite high case detection rates in Yunnan, China.

Delay in treating active tuberculosis (TB) impedes disease control by allowing ongoing transmission, and may explain the unexpectedly modest declines in global TB incidence. Even though China has achieved TB control targets under the global Directly Observed Treatment, Short course (DOTS) strategy, TB prevalence in western provinces, including Yunnan, is not decreasing. This cross-sectional study investigates whether prolonged delay in identifying and correctly treating TB patients, which is not routinely monitored, persists even when there is a well-functioning TB control programme and global targets are being met. Records of adult smear-positive pulmonary TB patients diagnosed with between 2006 and 2013 were extracted from the Yunnan Centre for Disease Control electronic database, which contains information on the entire population of TB patients managed across 129 diagnostic centres. Delay was investigated at three stages: delay to DOTS facility (period between symptom onset and first visit to at a CDC unit providing standardized treatment); delay to TB confirmation (period between reaching a CDC unit and confirmation of smear-positive TB) and delay to treatment (period between confirmation of TB and initiation of treatment). Data from 76 486 patients was analysed. Delay to reaching a DOTS facility was by far the largest contributor to total delay to treatment initiation. The median delay to reaching a DOTS facility, to TB confirmation and to treatment was 57 days (IQR 25-112), 2 days (IQR 1-6) and 1 day (IQR 0-1) respectively. Prolonged delays to reaching a facility providing standardized TB care occurred in a substantial subset of the population despite all TB control targets being met; overall, 32% (24 676) of patients experienced a delay of more than 90 days to reaching a DOTS facility. Policies that focus on reducing delays in accessing appropriate health services, rather than only on increasing overall case-detection rates, may result in greater progress towards reducing TB incidence.

Increased risk of tuberculosis among health care workers in Samara Oblast, Russia: analysis of notification data.

SETTING: Samara Oblast, Russia. OBJECTIVE: To compare the rates of tuberculosis (TB) in health care workers (HCWs) working in TB services, general health services (GHS) and the general population in a region of the Russian Federation. DESIGN: Analysis of notification rates of TB among HCWs, GHS workers and the general population during the 9-year period from 1994 to 2002. RESULTS: During 1994-2002, TB incidence among staff employed at the TB services in Samara Oblast was ten times higher than among the general population, reaching 741.6/100 000 person years at risk. Staff working at in-patient TB facilities were found to be at highest risk, with an incidence rate ratio of 17.7 (95% CI 11.6-27.0) compared to HCWs at the GHS. CONCLUSIONS: HCWs at TB services in the Russian Federation are at substantially increased risk for TB, suggesting significant risks from nosocomial transmission. Control of institutional spread of TB in the Russian Federation is an area that requires urgent attention, especially given the epidemic of human immunodeficiency virus that Russia is currently witnessing.

Social factors influencing hospital utilisation by tuberculosis patients in the Russian Federation: analysis of routinely collected data.

OBJECTIVE: To establish whether admissions, discharges and hospital utilisation for tuberculosis (TB) in Russia are independent of sex, age, disability and employment status. STUDY POPULATION AND METHODS: Analysis of hospital admissions, discharges and in-patient utilisation using routinely collected data in Samara Region of the Russian Federation. RESULTS: Male, unemployed and disabled adults were significantly more likely to be hospitalised (P < 0.001). The unemployed and pensioners were more likely to have multiple admissions. Unemployed adults were more likely to have longer average lengths of stay per admission (P < 0.001), with a cumulative length of stay for unemployed and disabled adults significantly greater than for employed adults and adults with no disability. Interruption of hospital care was significantly more frequent in male, disabled and unemployed patients (P < 0.001). CONCLUSIONS: Socio-economic factors influence hospital admission patterns and the length of stay for patients when hospitalised, as the providers of TB services attempt to mitigate the lack of social care provision for patients. For the WHO DOTS strategy to be effectively implemented and sustained in the Russian Federation health system, social sector linkage issues need to be addressed.

The effect of cigarette smoking on the development of AIDS in HIV-1-seropositive individuals.

OBJECTIVE: To determine whether HIV-1-seropositive cigarette smokers progress more rapidly to AIDS than HIV-1-seropositive non-smokers. SETTING: The genitourinary medicine outpatient department of St Mary's Hospital, London, which is a London University teaching hospital (tertiary care centre). SUBJECTS AND DESIGN: Case series of 84 individuals with AIDS who provided accurate details of their smoking habits before their AIDS-defining diagnosis. MAIN OUTCOME MEASURE: Progression time to AIDS in relation to smoking habit. RESULTS: Progression time to AIDS (all diagnoses) was significantly reduced in HIV-1-seropositive smokers: median time to AIDS was 8.17 months for smokers (n = 43) and 14.50 months for non-smokers (n = 41) (P = 0.003). Smokers developed Pneumocystis carinii pneumonia (PCP) more rapidly than non-smokers, with a median time to PCP of 9.0 months, compared with 16.0 months for non-smokers (P = 0.002). Smoking had no significant effect on progression time to AIDS when not due to PCP. CONCLUSION: Cigarette smoking by HIV-1-seropositive individuals is associated with a more rapid development of AIDS and should be discouraged.

Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented. SETTING: Hospital-based HIV units. PATIENTS: Twenty-three HIV-1-seropositive patients. RESULTS: Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically. CONCLUSION: AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

Nocardia infection in AIDS: a clinical and microbiological challenge.

A case of Nocardia asteroides pneumonia was diagnosed after death in a patient with AIDS. Six sputum cultures and one bronchoalveolar lavage fluid contained no pathogens, and no growth was obtained from one pleural fluid aspirate. None of these specimens was incubated for more than two days. Extended incubation for mycobacteria also failed to help in the diagnosis. N asteroides was isolated from pus taken from the lung cavity during the post mortem examination. It is suggested that if nocardiosis enters the differential diagnosis all specimens should be cultured for at least two weeks and the use of selective media be considered. This case highlights the need for clinicians to maintain a high index of suspicion for this pathogen.

Disseminated pneumocystis carinii infection in AIDS.

Eight patients with AIDS and Pneumocystis carinii infection were studied. Protean manifestations were a feature not untypical of disseminated pneumocystosis. Aerosolised pentamidine as prophylaxis against P carinii pneumonia was ineffective at suppressing dissemination. The knowledge that extrapulmonary infection can occur has implications for the detection and treatment of, and prophylaxis against, P carinii infection. The survival of patients with disseminated pneumocystosis is particularly poor, and may be due to a lack of clinical awareness and consequent delay in diagnosis.

Screening for cytomegalovirus retinitis in HIV-positive and AIDS patients.

The ability of physicians to screen for AIDS-related cytomegalovirus retinitis (CMVR) was studied at a London AIDS centre. Patients had undergone direct ophthalmoscopy as part of their general examination by the physicians and were referred if fundal abnormalities were found, if a focus of extra-ocular CMVR was present or if the patient complained of visual symptoms. The provisional diagnoses of the physicians were compared with the final diagnoses of the ophthalmologists. Of 348 consecutive patients referred for an ophthalmic opinion, the physicians made the correct diagnosis in 69% of those referred with a provisional diagnosis of CMVR, in 66% of those with normal fundi and in 81% of those with toxoplasma chorioretinitis. Those cases of CMVR which were misdiagnosed by the physicians were usually mistaken for other retinal pathology which would warrant a specialist referral. Screening for CMVR in HIV-positive and AIDS patients may safely be undertaken by physicians familiar with the ocular manifestations of HIV-related disease.

Screening programmes for tuberculosis in new entrants across Europe.

Screening foreign-born groups with high rates of tuberculosis may help to ensure that they can benefit from early treatment and minimise onward transmission. In January 2003, we surveyed new entrant screening programmes in Europe. Of the 26 countries from whom a response was received, 13 (50%) conducted no specific tuberculosis screening. Of 13 countries with programmes, none conducted pre-entry screening, three conducted screening at ports of entry, and nine screened in other centres. All 13 principally screened refugees. All programmes used chest X-rays as a screening tool, but no two countries took the same specific clinical approach.

Tuberculosis control in Samara Oblast, Russia: institutional and regulatory environment.

SETTING: Tuberculosis control programme in Samara Oblast, Russia, funded in part by the government of the United Kingdom. OBJECTIVE: To identify and evaluate institutional and regulatory influences as well as incentives and disincentives that might be amenable to change in the promotion of the DOTS strategy. DESIGN: Multidisciplinary situational analysis through in-depth interviews of stakeholders and review of official federal and oblast documents. RESULTS: Interpretation of traditional notification data is complex because classification and reporting systems differ from World Health Organization principles. Regulations governing financing encourage lengthy hospitalisations and interventions, and provide few incentives to shift policy to ambulatory care. CONCLUSION: Accurate comparability of epidemiological trends and programmatic successes requires equivalent classification and reporting systems. If the DOTS strategy is to be sustainable, changes to financing systems will be needed.

Pneumothorax in patients with AIDS.

Eighty-seven inpatients were treated for 93 episodes of Pneumocystis carinii at St Mary's Hospital between January 1989 and December 1990. During this period, 298 patients with the acquired immunodeficiency syndrome (AIDS) were treated at this hospital. Sixteen episodes of pneumothorax occurred and 12 of these, occurring in ten patients, were unrelated to procedure. In six of 12 (50%), the pneumothoraces occurred concurrently with Pneumocystis carinii pneumonia (PCP) and in ten (83%) cases there was a past history of PCP. Bilateral pneumothorax occurred in five cases (42%). In seven (58%) of the cases, patients had been using aerosolized pentamidine as prophylaxis for PCP. This retrospective study confirms the association of pneumothorax with current PCP and also shows an association with previous infection. The use of aerosolized pentamidine was not associated with pneumothorax development. It is important to suspect pneumothorax in a patient with PCP who deteriorates acutely. The high incidence of bilateral pneumothorax means that pleurodesis should be considered early.

Mycobacterium malmoense infection in HIV positive patients.

Mycobacterium malmoense is a non-tuberculous mycobacterium which has previously been associated with underlying pulmonary pathology and depressed immunity. We describe two patients infected with human immunodeficiency virus from whom M. malmoense was isolated, and discuss its treatment and possible pathogenic role.

Mycobacterium kansasii and human immunodeficiency virus co-infection in London.

OBJECTIVES: although Mycobacterium kansasii infection has long been endemic in the U.K., the disease burden and characteristics of infection in the HIV-seropositive population has not been well documented. This study addresses these issues in an inner city population that comprises a quarter of all cases of acquired immunodeficiency syndrome (AIDS) reported in the U.K. METHODS: retrospective review of case notes from two inner London specialist HIV Units. RESULTS: twenty-nine cases of M. kansasii infection were identified, with case notes available for review in 26. Ten had pulmonary disease and nine had disseminated infection: a further seven patients appeared simply to be colonized (two respiratory and five gastrointestinal): M. kansasii was isolated from stool in over a third (nine of 26) of cases. Disseminated M. kansasii infection occurred in 0.44% of AIDS cases seen in our two units and all isolates were resistant to isoniazid ion vitro. A clinical response achieved in 11 of the 13 patients with M. kansasii-related disease who received anti-mycobacterial therapy. All four patients who relapsed following initial clinical response to therapy had received sub-optimal treatment. CONCLUSIONS: the incidence of disseminated M. kansasii infection in HIV-infected individuals in the U.K. is similar to that seen in those from high prevalence regions of the U.S.A., and anti-mycobacterial therapy leads to a clinical response in the majority of patients with HIV and M. kansasii co-infection. The frequent isolation of M. kansasii from the stool suggests that the gastrointestinal tract may be a significant source of disseminated infection.

HIV and tuberculosis co-infection in an inner London hospital--a prospective anonymized seroprevalence study.

OBJECTIVES: Since 1987 there has been an increase in tuberculosis notifications in the U.K., with this increase disproportionately affecting London. A recent national survey suggests that co-infection with HIV occurs in less than 5% of tuberculosis patients. This study asked if local co-infection rates in Inner London differed from the national results. METHODS: 157 consecutive patients starting antituberculous chemotherapy were venesected 2 weeks into treatment. Anonymized blood samples were screened for antibodies for HIV-1 and HIV-2 by enzyme-linked immunosorbent assay (ELISA). Epidemiological data were collected on each patient which was also coded before HIV test results were known. RESULTS: Of 157 patients commencing antituberculous therapy, 39 patients (24.8%) were found to be co-infected with HIV-1. HIV-negative and positive patients were similar in terms of age and sex. When 98 patients giving their country of origin as other than Europe were considered there were 22 co-infected with HIV (22.4%). Of the 39 HIV-positive identified in this study, 37 were also identified by our voluntary HIV testing programme. CONCLUSIONS: This study has shown that there may be very different rates of co-infection at a local level in the U.K. The local variation may be missed by national surveys and diverse local testing procedures. Anonymous testing identified only two patients with tuberculosis and HIV infection who were not identified by our voluntary HIV testing programme and this suggests that offering HIV tests to patients with tuberculosis is largely taken up by those at risk of HIV infection. Surveillance studies of this type are important in identifying marked local variation from the national pattern of HIV and Mycobacterium tuberculosis infection.

Cryptococcal infection in AIDS.

PIP: Cryptococcus neoformans is an important opportunist pathogen in human immunodeficiency virus (HIV) infection. Cryptococcal meningitis (CM) 3rd after primary HIV neuropathy an Toxoplasma gondii among infectious neurological diseases in AIDS patients. Extrapulmonary infection due to C. neoformans has occurred in up to 13% of patients. 86% of the Cryptococcus spp isolates in the US, Canada, and Japan are serotype A. Thousands of infection due to var neoformans have been reported in AIDS patients but only 3 cases of var gattii. Cryptococcal pneumonia meningitis appears in 63-84% of AIDS patients with symptoms of fever, headache, meningism, and photophobia. 17-37% of AIDS patients with Cm die during therapy, and only 18-30% live over 12 months. Treatment in patients without immunodeficiency deficit is with a combination of .3 mg/kg/day of amphotericin B and 150 mg/kg/day of flucytosine for 4 weeks. A dose of .5-.8 mg/kg/day amphotericin was most effective although renal toxicity occurred in 80% of patients. Fluconazole has been used since 1987: cerebrospinal fluid concentrations reached 60-80% in serum. Treatment in 8 of 14 patients receiving 400 mg/day fluconazole failed while it did not in 6 patients treated with .7 mg/kg/day of amphotericin for 7 days and flucytosine 100 mg/kg/day. 200 mg/bid itraconazole was given to 32 patients with cryptococcosis (24 CM cases and 26 AIDS victims) and 65% of CM patients improved clinically with negative cultures. The relapse of 2 of 106 patients taking 200 mg/day fluconazole and 13 of 77 patients taking 1 mg/kg/week amphotericin B occurred in maintenance therapy. CM was suppressed in 10 of 15 patients with 400 mg/kg itrazonazole. Prophylactic use of azole drugs in AIDS does not protect completely from CM although it reduced systemic fungal infections such as cryptococcosis.^ieng

The role of bronchoscopy in patients with HIV disease.

Pulmonary involvement is a frequent feature of patients infected with the human immunodeficiency virus (HIV). Pneumocystis carinii pneumonia (PCP) is still the commonest AIDS defining diagnosis despite the advent of effective prophylaxis and antiretroviral treatment. Other pulmonary manifestations of AIDS, including tuberculosis, may pose a greater problem in the future. The clinical manifestations of HIV-disease are many and varied, and changing as the disease is modified by therapeutic interventions. With specific and increasingly effective treatments the need for definitive diagnosis is obvious. Fibreoptic bronchoscopy is a well established tool for the diagnosis of HIV-related pulmonary complications. This article aims to give an account on the use of bronchoscopy in a unit providing care for many HIV seropositive patients.