High Human Immunodeficiency Virus Prevalence Setting Research Articles

Adherence to Community Acquired Pneumonia guideleines and patients outcomes in a peri-urban hospital in Natal, South Africa.

Community-acquired pneumonia (CAP) is an important cause of mortality and morbidity worldwide. This issue is further exacerbated by the Human Immunodeficiency Virus (HIV) epidemic. The study was a retrospective, clinical record review of hospitalized patients (18 years and older) with a diagnosis of LRTI between the 1st of January 2012 and 31 December 2012, descriptive and comparable analysis was performed. Number of patients was 274; 142 (51.8%) males. The commonest final diagnosis was Pulmonary Tuberclosis (PTB) in 131 (47.8%) and CAP in 127 (46.4%). The case fatality rate was 25.5% (70/274) and was significantly associated with HIV infection (77.4%) (p < 0,01), CD4 cell count ≤ 200 cells (96.3), final diagnosis of TB (65.7%) (p < 0.01), female sex (57%) (p < 0.01), confusion (50%) (p < 0.01), age of 65 years or more (29%) (p < 0.01). CURB-65 score (Confusion, Urea more than 7mmol/l, Respiratory rate (RR) ≥30 breaths /min, low blood pressure (less than 90 mmHg systolic and 60mmHg diastolic) and age ≥ 65 years) was only documented in 4 % (11/274) patients. Only 63 patients (23%) met the admission criteria of two or more points when the CURB-65 score was calculated. Failure to use the CURB-65 score resulted in an increase admission of patients presenting with LRTI. There was an increased case fatality rate in this high HIV prevalence setting.

Adiponectin DNA methylation in South African women with gestational diabetes mellitus: Effects of HIV infection.

DNA methylation is increasingly recognized as a potential biomarker of metabolic disease. However, there is limited information on the impact of human immunodeficiency virus (HIV) infection on the candidacy of DNA methylation to serve as molecular biomarkers. This study investigated the effect of HIV infection on DNA methylation patterns in the peripheral blood of South African women with (n = 95) or without (n = 191) gestational diabetes mellitus (GDM). DNA methylation levels at eight CpG sites in the adiponectin gene (ADIPOQ) promoter were measured using bisulfite conversion and pyrosequencing. Differences between HIV negative (-) and positive (+) women were observed. In HIV- women, methylation at CpG -3400 was lower in GDM+ women compared to those with normoglycemia (8.5-fold; p = 0.004), and was associated with higher fasting glucose (β-co-efficient = 0.973; p = 0.006) and lower adiponectin (β-co-efficient = -0.057; p = 0.014) concentrations. These associations were not observed in HIV+ women. In silico analysis showed that Transcription Factor AP2-alpha is able to bind to the altered CpG site, suggesting that CpG -3400 may play a functional role in the regulation of ADIPOQ expression. Our findings show that DNA methylation differs by HIV status, suggesting that HIV infection needs to be taken into consideration in studies exploring DNA methylation as a biomarker of GDM in high HIV prevalence settings.

Implementation of a PMTCT programme in a high HIV prevalence setting in Johannesburg, South Africa: 2002-2015.

BackgroundGreat strides have been made in decreasing paediatric human immunodeficiency virus (HIV) infections, especially in sub-Saharan Africa. In South Africa, new paediatric HIV infections decreased by 84% between 2009 and 2015. This achievement is a result of a strong political will and the rapid evolution of the country’s prevention of mother-to-child transmission (PMTCT) guidelines.ObjectivesIn this paper we report on the implementation of a large PMTCT programme in Soweto, South Africa.MethodsWe reviewed routinely collected PMTCT data from 13 healthcare facilities, for the period 2002–2015. Antiretroviral therapy (ART) coverage among pregnant women living with HIV (PWLHIV) and the mother-to-child transmission (MTCT) rate at early infant diagnosis were evaluated.ResultsIn total, 360 751 pregnant women attended the facilities during the review period, and the HIV prevalence remained high throughout at around 30%. The proportion of PWLHIV presenting with a known HIV status increased from 14.3% in 2009 when the indicator was first collected to 45% in 2015, p < 0.001. In 2006, less than 10% of the PWLHIV were initiated on ART, increasing to 88% by 2011. The MTCT rate decreased from 6.9% in 2007 to under 1% from 2013 to 2015, p < 0.001.ConclusionThe achievements in decreasing paediatric HIV infections have been hailed as one of the greatest public health achievements of our times. While there are inherent limitations with using routinely collected aggregate data, the Soweto data reflect progress made in the implementation of PMTCT programmes in South Africa. Progress with PMTCT has, however, not been accompanied by a decline in HIV prevalence among pregnant women.

Presentation and outcome of patients with intracranial tuberculoma in a high HIV prevalence setting

SETTING: A referral hospital in South Africa.OBJECTIVE: To describe the clinical presentation, serial brain imaging findings during treatment and outcome of patients with intracranial tuberculoma in a high human immunodeficiency virus (HIV) prevalence setting.DESIGN: This was a retrospective observational study conducted over a 12.5-year period. Records of adults (age ≥18 years) who presented with neurological TB were screened. We included patients with tuberculoma in whom sequential brain imaging was performed.RESULTS: Of 66 patients enrolled, HIV status was known in 61; 47 (71%) were HIV-infected and 14 (21%) were non-HIV-infected. Clinical and imaging findings and outcomes were similar between these groups. Persistent tuberculoma was present at 18 months follow-up in 20/41 (49%) patients who underwent repeat imaging at that timepoint; those with persistent tuberculoma were more likely to have persisting neurological abnormalities (85% vs. 52%; P = 0.043). Larger tuberculoma size at presentation (≥3 cm) was the only factor significantly associated with tuberculoma persistence (multivariable logistic regression, OR 19.9, 95%CI 1.27-309.68; P = 0.033).CONCLUSION: Tuberculoma is a severely disabling TB manifestation regardless of HIV coinfection, with half of patients showing radiologically persistent lesions at 18 months follow-up. Large size of tuberculoma at presentation heralds lower chance of its resolution within 18 months.

Screening tools to exclude active pulmonary TB in high TB burden countries: systematic review and meta-analysis.

<sec> <title>OBJECTIVE</title> To examine the use of symptoms, chest X-ray (CXR) abnormalities, and combinations of symptoms and CXR in excluding active pulmonary tuberculosis (TB) before treating for latent tuberculous infection (LTBI) in high TB burden countries. </sec> <sec> <title>METHODS</title> We updated a systematic review and meta-analysis of studies on the sensitivities, specificities, predictive values, diagnostic odds ratios and areas under the curve for index tests. The analysis was conducted using the hierarchical summary receiver operating characteristic method in R software. </sec> <sec> <title>RESULTS</title> We included 24 publications in the systematic review and meta-analysis. 'Any CXR abnormality' had the highest sensitivity (94.1%, 95%CI 85.8-97.7) among all index tests. 'CXR abnormality suggestive of TB' had a higher specificity (92.2%, 95%CI 89.7-94.1) than 'any CXR abnormality' (86.8%, 95%CI 79.7-91.7). The sensitivity for 'any TB symptom' was 73.0% (95%CI 64.1-80.4), while 'prolonged cough' of ≥2 weeks had a specificity of 94.3% (95%CI 92.2-95.9). There was no significant difference in the sensitivity and specificity of all screening tools stratified by human immunodeficiency virus (HIV) settings, with the exception of 'CXR abnormality suggestive of TB', which had a significantly higher sensitivity in low than in high HIV prevalence settings (effect estimate 2.26, 95%CI 0.69-3.82; P = 0.002). </sec> <sec> <title>CONCLUSION</title> In countries with a high TB burden, the absence of any TB symptom and any CXR abnormality can be used to exclude active pulmonary TB before initiating treatment for LTBI in household contacts aged ≥5 years of patients with bacteriologically confirmed pulmonary TB. </sec>.

A model to promote the uptake of male circumcision as an HIV-preventive measure in high HIV and low male circumcision prevalence settings.

BackgroundHuman immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) remain the leading global burden of disease, especially in Southern Africa. As such, efforts to develop innovative preventive and curative measures continue to be a global priority. Of late, the World Health Organization recognised and recommended mass male circumcision (MC) as an adjunct HIV-preventive measure in 14 selected sub-Sahara African countries. However, despite efforts to promote the uptake of MC in these countries, the uptake remains significantly below set targets.AimThe purpose of this article is to describe the process that was followed in developing, describing and evaluating a model to promote the uptake of MC as an HIV-preventive measure in high HIV and low MC settings.SettingThe model is designed for all settings of high HIV and low MC prevalence.MethodA theory-generative, qualitative, exploratory, descriptive and contextual research design was used. The process involved four distinct steps, namely concept analysis, description of relationship statements, and description and evaluation of the model using the criteria of clarity, simplicity, generality, accessibility and importance.ResultsThe central concept was identified as ‘promote the uptake of MC’, and three integral constituents were identified for the process, such as transforming men’s mindsets about MC, facilitating accessibility and utilisation of MC services, and maintaining a supportive social system. These formed the basis for the model.ConclusionThe model provides a framework of reference for healthcare providers in promoting the uptake of MC as an HIV-preventive measure in high HIV and low MC settings.

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Epidemiology of Severe Acute Respiratory Illness and Risk Factors for Influenza Infection and Clinical Severity among Adults in Malawi, 2011-2013.

.Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged ≥ 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7–16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83–6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57–5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35–4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43–0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36–0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35–2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17–7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings.

Utilization and Clinical Value of Diagnostic Modalities for Tuberculosis in a High HIV Prevalence Setting.

Human immunodeficiency virus (HIV) infection is a major risk factor for the development of active tuberculosis (TB), one of the deadliest infectious diseases globally. The high mortality associated with the disease can be reduced by early diagnosis and prompt antituberculous treatment initiation. Facilities in TB-endemic regions are increasing the use of nucleic acid amplification (e.g., GeneXpert), which provides rapid results but may have suboptimal sensitivity in HIV-associated TB. Our objective was to evaluate the current practices for TB diagnosis at Edendale Hospital, a large regional hospital in KwaZulu-Natal, South Africa-a TB-endemic region with high HIV prevalence. In this cross-sectional study, all adult inpatients newly started on TB treatment at Edendale were identified over a 6-week period. Demographics, clinical information, diagnostic test results, and outcomes were documented. Pulmonary TB (PTB), extrapulmonary TB (EXTB), and PTB + EXTB were defined as disease evidence in the lungs, other organs, or both, respectively. Ninety-four cases were identified, of which 83% were HIV-associated. Only 30% of all TB patients were microbiologically confirmed, consisting of 7/16 (44%) HIV-uninfected and 21/78 (27%) HIV-infected TB patients. Smear microscopy and mycobacterial culture were seldom ordered. Ultrasound was performed in about one-third of suspected EXTB cases and was valuable in identifying abdominal TB. In this clinical setting with a high incidence of HIV-associated TB, TB diagnosis was more commonly based on clinical assessment and imaging results than on mycobacterial gold standard test confirmation.

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. NCT01898754.

Incidence of tuberculosis meningitis in a high HIV prevalence setting: time-series analysis from 2006 to 2011.

This study was undertaken at a tertiary hospital in Soweto, a peri-urban low-middle income setting. Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis. To describe the incidence, mortality and clinical features of TBM in human immunodeficiency virus (HIV) infected and non-infected children in South Africa from 2006 to 2011. A retrospective, cross-sectional descriptive study. Electronic databases and individual patient records of all children with a discharge diagnosis of TBM were reviewed to yield incidence rate ratios (IRR) in HIV-infected and non-infected children. Clinical, laboratory and radiological characteristics were compared between HIV-infected and non-infected children with TBM. Overall TBM incidence per 100 000 population in 2006 was 6.9 (95%CI 4.4-10.3) and 9.8 (95%CI 6.9-13.6) in 2009, but had subsequently declined to 3.1 (95%CI 1.6-5.5) by 2011. There was a significant reduction in the IRR of TBM among HIV-infected children (IRR 0.916, P = 0.036). The overall case fatality ratio was 6.7%. Clinical features, cerebrospinal fluid and computed tomography brain findings were similar in HIV-infected and non-infected children. TBM incidence decreased over the study period from 2006 to 2011, and was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa.

The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n = 46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR) and for bacteria and fungi by culture. Based on clinical history, disease characteristics and laboratory results, 29 (63 %) patients were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and 17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively. Among clinically defined viral keratitis cases, a negative viral swab was predominantly (93 %) observed in cases with subepithelial inflammation and was significantly associated with an increased duration of symptoms (p = 0.003). The majority of bacteria cultured were Gram-positive (24/35), including Staphylococcus epidermidis and S. aureus. Viral aetiology was significantly associated with a history of herpes zoster ophthalmicus (p < 0.001) and a trend was observed between viral aetiology and HIV infection (p = 0.06). Twenty-one (47 %) keratitis cases were complicated by anterior uveitis, of which 18 (86 %) were HIV-infected cases with viral keratitis. The data implicate a high prevalence of herpetic keratitis, in part complicated by bacterial superinfection and/or uveitis, in HIV-infected individuals presenting with infectious keratitis in rural South Africa.

Undiagnosed TB in adults dying at home from natural causes in a high TB burden setting: a post-mortem study.

A high proportion of deaths in Africa occur at home, where cause of death (CoD) is often unknown. We ascertained undiagnosed pulmonary tuberculosis (TB) by performing limited autopsies in adults dying at home in whom there was no apparent CoD. Mortuaries in Matlosana, South Africa, identified potentially eligible adults with no ante-mortem diagnosis and/or no recent hospital admission. A questionnaire was administered to family members. Bilateral lung core biopsies and modified bronchoalveolar lavage (BAL) were performed. The biopsies were examined histologically and submitted with BAL aspirates for mycobacterial culture (MGIT(TM)) and Xpert(®) MTB/RIF testing. Human immunodeficiency virus (HIV) testing was not performed. Of 162 families approached, 28 refused and 29 of the deceased were on or had recently stopped anti-tuberculosis treatment; 85 were included. All were Black and 53% were men. The median age was 57 years (interquartile range [IQR] 44-66) and median symptom duration (mainly cough) was 63 days (IQR 14-112). Laboratory evidence of TB was found in 27 (31.8%); 21 were Xpert-positive, 23 were MGIT-positive and 14 had histological evidence consistent with active TB. In this high HIV prevalence setting, a quarter of the home deaths had evidence of undiagnosed, likely infectious TB, suggesting that TB-related mortality is under-ascertained and under-reported, with serious implications for TB control in high TB burden settings.

Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis.

South Africa has a large burden of extensively drug-resistant tuberculosis (XDR-TB); only 15% of XDR-TB patients have successful outcomes. To describe the safety and effectiveness of bedaquiline (BDQ) in the South African BDQ Clinical Access Programme. An interim cohort analysis. Of the first 91 patients enrolled between March 2013 and July 2014 (with follow-up until August 2014), 54 (59%) were human immunodeficiency virus (HIV) infected. The median CD4 count was 239 cells/μl, and all patients were on antiretroviral therapy (ART) at initiation of BDQ; 33 had XDR-TB, 41 were pre-XDR-TB with fluoroquinolone resistance and 17 were pre-XDR-TB with resistance to an injectable. Of the 91 patients, 58 (64%) had completed 24 weeks of BDQ, 28 were still on BDQ, 3 were lost to follow-up, 1 had died and 1 had BDQ withdrawn following atrial fibrillation. Of the 63 patients with 6 months follow-up, 48 (76%) had either culture-converted or remained culture-negative after initiation of BDQ. QTcF was monitored monthly and exceeded 500 ms in three participants; this resolved in all three. Interim safety and culture conversion outcomes for patients accessing BDQ in South Africa, including HIV-infected patients on ART and patients with pre-XDR- and XDR-TB, suggest that BDQ may be both efficacious and safe.

How can mathematical models advance tuberculosis control in high HIV prevalence settings?

SUMMARYExisting approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly.

Hepatitis B and HIV co-infection in pregnant women: indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting.

Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of reproductive age is of clinical and public health importance because these women constitute a significant reservoir for horizontal and perinatal HBV transmission. Childhood HBV vaccination from 6 weeks of age protects most children against chronic HBV infection. However, infants born to HBV/HIV co-infected women are more likely to be infected perinatally, with an increased risk of chronic hepatitis, than infants born to HBV mono-infected women. The aim of our study was to establish the prevalence of HBV infection and HBV/HIV co-infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal HBV screening and childhood immunisation policies in South Africa. Stored plasma specimens obtained from 570 pregnant women were tested for hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load. The antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3% (95% confidence interval (CI) 3.4 - 7.1), respectively. Overall, 3.1% (95% CI 1.7 - 4.6) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the HBV DNA load being significantly higher in co-infected women. We report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in pregnant women from this HIV-endemic region. Routine antenatal HBV screening will allow early identification of neonates who require HBV active-passive immunoprophylaxis at birth. This strategy, together with antenatal antiretrovirals, will reduce the risk of perinatal HBV transmission, especially in high-risk HBV/ HIV co-infected pregnant women.

Mortality Associated With Seasonal and Pandemic Influenza and Respiratory Syncytial Virus Among Children &lt;5 Years of Age in a High HIV Prevalence Setting—South Africa, 1998–2009

There are few published data describing the mortality burden associated with influenza and respiratory syncytial virus (RSV) infection in children in low- and middle-income countries and particularly from Africa and settings with high prevalence of human immunodeficiency virus (HIV). We modeled the excess mortality attributable to influenza (seasonal and pandemic) and RSV infection by applying Poisson regression models to monthly all-respiratory and pneumonia and influenza deaths, using national influenza and RSV laboratory surveillance data as covariates. In addition, we estimated the seasonal influenza- and RSV-associated deaths among HIV-infected and -uninfected children using Poisson regression models that incorporated HIV prevalence and highly active antiretroviral therapy coverage as covariates. In children <5 years of age, the mean annual numbers of seasonal influenza- and RSV-associated all-respiratory deaths were 452 (8 per 100 000 person-years [PY]) and 546 (10 per 100 000 PY), respectively. Infants <1 year of age experienced higher mortality rates compared with children 1-4 years of age for both influenza (22 vs 5 per 100 000 PY) and RSV (35 vs 4 per 100 000 PY). HIV-infected compared with HIV-uninfected children <5 years of age were at increased risk of death associated with influenza (age-adjusted relative risk [aRR], 11.5; 95% confidence interval [CI], 9.6-12.6) and RSV (aRR, 8.1; 95% CI, 6.9-9.3) infection. In 2009, we estimated 549 (11 per 100 000 PY) all-respiratory influenza A(H1N1)pdm09-associated deaths among children aged <5 years. Our findings support increased research efforts to guide and prioritize interventions such as influenza vaccination and HIV prevention in low- and middle-income countries with high HIV prevalence such as South Africa.

Predictors of delay in the diagnosis and treatment of suspected tuberculosis in HIV co-infected patients in South Africa

In South Africa, the majority of tuberculosis (TB) patients are co-infected with the human immunodeficiency virus (HIV), and delays in diagnosis and treatment likely exacerbate morbidity and mortality. To determine predictors of delays in the diagnosis and treatment of hospitalised suspected pulmonary TB patients co-infected with HIV. Post-analysis of data collected in a three-centre prospective cohort of in-patients clinically diagnosed with active TB in three hospitals in South Africa between 2006 and 2009 during the first 24 h of admission. Delay was assessed by asking time of first symptoms and any prior health-seeking behaviour for this episode of illness. Data from a total of 891 participants with a median age of 36 years and a CD4 count of 67 cells/mm(3) were analysed. Median patient, system and total delays were respectively 28, 1 and 28 days. Unemployment, treatment at Tshepong Hospital, alcohol consumption, crowding index, seeking prior treatment, cotrimoxazole treatment and WHO Stage 4 disease predicted prolonged total delay. Patient delay in seeking care for TB in this high HIV prevalence setting is substantial. Factors identified with delay could be used to develop interventions to improve care seeking and earlier diagnosis of TB.

Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality [State of the art series. Active case finding/screening. Number 5 in the series

Twenty years of sky-high tuberculosis (TB) incidence rates and high TB mortality in high human immunodeficiency virus (HIV) prevalence countries have so far not been matched by the same magnitude or breadth of responses as seen in malaria or HIV programmes. Instead, recommendations have been narrowly focused on people presenting to health facilities for investigation of TB symptoms, or for HIV testing and care. However, despite the recent major investment and scale-up of TB and HIV services, undiagnosed TB remains highly prevalent at community level, implying that diagnosis of TB remains slow and incomplete. This maintains high transmission rates and exposes people living with HIV to high rates of morbidity and mortality. More intensive use of TB screening, with broader definitions of target populations, expanded indications for screening both inside and outside of health facilities, and appropriate selection of new diagnostic tools, offers the prospect of rapidly improving population-level control of TB. Diagnostic accuracy of suitable (high throughput) algorithms remains the major barrier to realising this goal. In the present study, we review the evidence available to guide expanded TB screening in HIV-prevalent settings, ideally through combined TB-HIV interventions that provide screening for both TB and HIV, and maximise entry to HIV and TB care and prevention. Ideally, we would systematically test, treat and prevent TB and HIV comprehensively, offering both TB and HIV screening to all health facility attendees, TB households and all adults in the highest risk communities. However, we are still held back by inadequate diagnostics, financing and paucity of population-impact data. Relevant contemporary research showing the high need for potential gains, and pitfalls from expanded and intensified TB screening in high HIV prevalence settings are discussed in this review.

High risk of drug-resistant tuberculosis when first-line therapy fails in a high HIV prevalence setting

Lesotho national multidrug-resistant tuberculosis (MDR-TB) program. To determine the prevalence of drug-resistant TB (DR-TB) among patients registered for MDR-TB treatment after failure or suspected failure of the standard 6-month regimen for new TB patients (Category I). We conducted a retrospective cohort study of patients registered for MDR-TB treatment following failure or suspected failure of Category I. A total of 76 patients were included in the analysis, including 51 Category I treatment failures and 25 suspected Category I treatment failures. The prevalence of resistance to any drug was 92% among the treatment failures and 72% among the suspected failures. The proportion of MDR-TB was respectively 78% and 28% among the treatment failures and suspected failures. Among the subgroup of human immunodeficiency virus (HIV) positive patients, the proportion of MDR-TB was 84% among failures and 23% among suspected failures. DR-TB and MDR-TB were common among patients in whom Category I failed. Early initiation of empiric second-line anti-tuberculosis treatment while awaiting culture and drug susceptibility testing (DST) results should be considered for HIV-negative and -positive patients who have failed first-line anti-tuberculosis treatment; patients suspected to be failing a first-line regimen should undergo DST at the end of the intensive phase.