Performance of Xpert® MTB/RIF and Determine™ TB-LAM Ag in HIV-infected adults in peri-urban sites in Zambia.

SETTING: Peri-urban health facilities providing HIV and TB care in Zambia. OBJECTIVE: To evaluate 1) the impact of Xpert® MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. DESIGN: Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. RESULTS: Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm3 vs. 31.7% overall. CONCLUSION: Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.

Poor continuity of care for TB diagnosis and treatment in Zambian Prisons: a situation analysis.

OBJECTIVES: Prisons act as infectious disease reservoirs. We aimed to explore the challenges of TB control and continuity of care in prisons in Zambia. METHODS: We evaluated treatment outcomes for a cohort of inmates diagnosed with TB during a TB REACH funded screening programme initiated by the Zambia Prisons Service and the Centre for Infectious Disease Research in Zambia. RESULTS: Between October 2010 and September 2011, 6282 inmates from six prisons were screened for TB, of whom 374 (6.0%) were diagnosed. TB treatment was initiated in 345 of 374 (92%) inmates. Of those, 66% were cured or completed treatment, 5% died and 29% were lost to follow-up. Among those lost to follow-up, 11% were released into the community and 13% were transferred to other prisons. CONCLUSIONS: Weak health systems within the Zambian prison service currently undermines continuity of care, despite intensive TB screening and case-finding interventions. To prevent TB transmission and the development of drug resistance, we need sufficient numbers of competent staff for health care, reliable health information systems including electronic record keeping for prison facilities, and standard operating procedures to guide surveillance, case-finding and timely treatment initiation and completion.

Automatic versus human reading of chest X-rays in the Zambia National Tuberculosis Prevalence Survey.

SETTING: Tuberculosis (TB) prevalence survey in Zambia between 2013 and 2014. OBJECTIVE: To compare the performance of automatic software (CAD4TB 5) in chest X-ray (CXR) reading with that of field (general practitioners) and central (radiologists) readers. DESIGN: A retrospective study comparing the performance of human and automatic reading was conducted. Two scenarios for central reading were evaluated: abnormalities not consistent with TB were considered to be 'normal' or 'abnormal'. Sputum culture was defined as the reference standard. Measures derived from receiver operating characteristic analysis were used to assess readers' performances. RESULTS: Of 46 099 participants, 23 838 cases included all survey information; of these, 106 cases were culture-confirmed TB-positive. The performance of CAD4TB 5 was similar to that of field and central readers. Although there were significant differences in specificity when compared with field readings (P = 0.002) and central readings considering the first scenario (P < 0.001), these differences were not substantial (93.2% vs. 92.6% and 98.4% vs. 99.6%, respectively).CONCLUSIONp: The performance of automatic CXR readings is comparable with that of human experts in a TB prevalence survey setting using culture as reference.

What happened to patients with RMP-resistant/MDR-TB in Zambia reported as lost to follow-up from 2011 to 2014?

SETTING: University Teaching Hospital, Lusaka, and Ndola Central Hospital, Ndola, Zambia, which implemented active tracing of multidrug-resistant tuberculosis (MDR-TB) patients reported as lost to follow-up (LTFU). OBJECTIVE: To determine 1) the number of patients treated for MDR-TB between 2011 and 2014; 2) the number, proportion, month when LTFU and characteristics of patients registered as LTFU; and 3) final outcomes observed following active patient tracing. DESIGN: Retrospective cohort study. RESULTS: Of 184 patients treated for confirmed MDR-TB, 76 (41%) were reported as LTFU. From 2011 to 2014, the proportions reported each year as LTFU were respectively 21%, 47%, 51% and 39%. Of patients who were LTFU, 43 (57%) had stopped attending the clinic during the intensive phase. These patients were predominantly male, aged 15-44 years, had pulmonary disease and had failed previous treatment. Of 57 (75%) patients with known human immunodeficiency virus (HIV) status, 42 (74%) were HIV-positive, 57% of whom were on antiretroviral treatment. After active patient tracing, 29 (38%) patients could not be found and the observed outcome remained LTFU. Of the remaining 47 patients, 29 (62%) were alive and had completed or were still on treatment, 14 (30%) were alive but had stopped treatment and 4 (8%) had died. CONCLUSION: Zambia has been underreporting its favourable outcomes for MDR-TB treatment and should continue with active tracing of LTFU patients.

High prevalence of tuberculosis in newly enrolled HIV patients in Zambia: need for enhanced screening approach.

SETTING: Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed. OBJECTIVE: We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees. DESIGN: Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert(®) MTB/RIF testing was performed retrospectively. RESULTS: From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/µl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture-negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific. CONCLUSIONS: High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population.

Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.

SETTING: Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. OBJECTIVE: To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. DESIGN: Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. RESULTS: A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. CONCLUSION: TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.

Integrating active tuberculosis case finding in antenatal services in Zambia.

SETTING: Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia. OBJECTIVE: To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings. DESIGN: Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence. RESULTS: All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive. CONCLUSION: There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.

TB and HIV in the Central African region: current knowledge and knowledge gaps.

PURPOSE: Reliable and comprehensive data on the HIV/AIDS and TB co-pandemics from Central Africa remain scarce. This systematic review provides a comprehensive overview on current and past research activities in the region and provides a basis for future research work to close knowledge gaps. METHODS: The scientific literature was searched for publications meeting the following search terms: "tuberculosis" or "HIV" or "acquired immunodeficiency syndrome", combined with "Central Africa", or the names of individual countries within the region. Original studies, reviews and case series were included, and a selection of relevant articles was made. RESULTS: Most research in the field of HIV and TB has been conducted in Cameroon, where the epidemics have been described fairly well. The Democratic Republic of Congo ranked second on the amount of publications, despite the civil wars over the past several decades. Very little has been published on HIV and TB in the other countries, possibly due to the poor infrastructure of health care systems, lack of scientific capacity building or shortage of laboratory equipment. CONCLUSIONS: Despite the relatively high burden of HIV and TB in the Central African region, the amount of research activities on these topics is limited. A better understanding of the co-epidemics in this region is urgently needed. The occurrence of opportunistic infections, treatment complications and drug resistance in TB and HIV need to be better described; the failure of public health systems needs to be understood, and research infrastructure needs to be developed. Only then will it be possible to turn the tide against the HIV and TB epidemics in this region.

Scale-up of TB and HIV programme collaborative activities in Zambia - a 10-year review.

OBJECTIVE: To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. METHODS: Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010. RESULTS: The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. CONCLUSIONS: The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).

Trials and tribulations of an African-led research and capacity development programme: the case for EDCTP investments.

We describe the initiation and establishment of The University of Zambia - University College London Medical School (UNZA-UCLMS) Research and Training Project, an entirely African scientist-led, south-north partnership. In its 16 year existence, the project, by successfully obtaining competitive grant funding, has transformed itself into one of Africa's most productive African-led R&D programmes with training and visible research outputs. The project serves as a role model and now networks R&D and training activities with six southern African (10 institutions) and six European countries. This project case study illustrates that deep commitment is essential for success and that the factors which facilitate success in R&D in Africa need to be evaluated. The long-term prospects for sustaining the UNZA-UCLMS Project appear bright and are dependent on several factors: the ability to retain trained African scientists; obtaining continued competitive or donor grant funding support; and serious investment by the African governments involved. The recent 255 million Euros EDCTP investment in sub-Saharan Africa through south-north partnerships is expected to enhance existing African-led R&D programmes. African governments and scientists must rise to the challenge.