Clinical presentations and outcomes of HIV-1 and HIV-2 among infected children in Guinea-Bissau: a nationwide study.

OBJECTIVES: Disease progression, loss to follow-up, and mortality of HIV-2 compared with HIV-1 in children is not well understood. This is the first nationwide study reporting outcomes in children with the two HIV types in Guinea-Bissau. STUDY DESIGN: Nationwide retrospective follow-up study. METHODS: This is a retrospective follow-up study among HIV-infected children <15 years at nine ART centers from 2006 to 2021. Baseline parameters and disease outcomes for children with HIV-2 and HIV-1 were compared. RESULTS: The annual number of children diagnosed with HIV peaked in 2017. HIV-2 (n = 64) and HIV-1 (n = 1945) infected children were different concerning baseline median age (6.5 vs 3.1 years, P < 0.01), but had similar levels of severe immunodeficiency (P = 0.58) and severe anemia (P = 0.26). Within the first year of follow-up, 36.3% were lost, 5.9% died, 2.7% had transferred clinic, and 55.2% remained for follow-up. Mortality (HR = 1.05 95% CI: 0.53-2.08 for HIV-2) and attrition (HR = 0.86 95% CI: 0.62-1.19 for HIV-2) rates were similar for HIV types. CONCLUSIONS: The decline in children diagnosed per year since 2017 is possibly due to lower HIV prevalence, lack of HIV tests, and the SARS-CoV-2 epidemic. Children with HIV-2 were twice as old as HIV-1 infected when diagnosed, which suggests a slower disease progression. However, once they develop immunosuppression mortality is similar.

SARS-CoV-2 seroprevalence among people living with HIV in Guinea-Bissau.

OBJECTIVES: In low-income countries with poor SARS-CoV-2 monitoring and high HIV burden, the prevalence of SARS-CoV-2 is scarcely studied in people living with HIV (PLWH). We set out to measure SARS-CoV-2 seroprevalence in this group. STUDY DESIGN: Serosurvey of SARS-CoV-2 in PLWH. METHODS: We measured IgG/IgM antibodies using point-of-care rapid tests in 294 PLWH with HIV-1, HIV-2 or HIV-1/2 dual infection at an HIV clinic in Guinea-Bissau between June 1, 2021, and October 1, 2021. RESULTS: Unvaccinated PLWH (n = 195), constituting 66% of the total study population, had a seroprevalence of SARS-CoV-2 antibodies of 27.7%. Of SARS-CoV-2 seropositive unvaccinated PLWH, 71.2% reported no symptoms of COVID-19 since the start of the epidemic up to the inclusion date. Among all participants, 90.1% reported never having been tested for SARS-CoV-2 by any test (n = 292). Six participants reported a household death, corresponding to a crude annual death rate of 3.3 per 1000 people. CONCLUSIONS: Despite a low number of officially registered cases of SARS-CoV-2 in Bissau, we found a high seroprevalence of SARS-CoV-2 of 27.7% in unvaccinated PLWH. Coupled with few ever tested for SARS-CoV-2, it indicates that official PCR testing likely underestimates prevalence and that SARS-CoV-2 monitoring is challenged for PLWH. The low number of symptoms from seropositives may stem from survival bias, some effect of herd immunity or, coupled with a low crude annual death rate, that disease symptomatology and severity could be lower than expected.

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options.

Despite advances in the treatment quality of HIV throughout the world, several countries are still facing numerous obstacles in delivering HIV treatment at a sufficiently high quality, putting patients' lives in jeopardy. The aim of this status article is to give an overview of HIV treatment outcomes in the West African country, Guinea-Bissau, and to assess how newer treatment strategies such as long-acting injectable drugs or an HIV cure may limit or stop the HIV epidemic in this politically unstable and low-resource setting. Several HIV cohorts in Guinea-Bissau have been established and are used as platforms for epidemiological, virological, immunological and clinical studies often with a special focus on HIV-2, which is prevalent in the country. The Bandim Health Project, a demographic surveillance site, has performed epidemiological HIV surveys since 1987 among an urban population in the capital Bissau. The Police cohort, an occupational cohort of police officers, has enabled analyses of persons seroconverting with estimated times of seroconversion among HIV-1 and HIV-2-infected individuals, allowing incidence measurements while the Bissau HIV Cohort and a newer Nationwide HIV Cohort have provided clinical data on large numbers of HIV-infected patients. The HIV cohorts in Guinea-Bissau are unique platforms for research and represent real life in many African countries. Poor adherence, lack of HIV viral load measurements, inadequate laboratory facilities, high rates of loss to follow-up, mortality, treatment failure and resistance development, are just some of the challenges faced putting the goal of "90-90-90″ for Guinea-Bissau well out of reach by 2020. Maintaining undetectable viral loads on treatment as a prerequisite of a cure strategy seems not possible at the moment. Thinking beyond one-pill-once-a-day, long-acting antiretroviral treatment options such as injectable drugs or implants may be a better treatment option in settings like Guinea-Bissau and may even pave the way for an HIV cure. If the delivery of antiretroviral treatment in sub-Saharan Africa in a sustainable way for the future should be improved by focusing on existing treatment options or through focusing on new treatment options remains to be determined.

The challenge of discriminating between HIV-1, HIV-2 and HIV-1/2 dual infections.

OBJECTIVES: Discrimination between HIV-1 and HIV-2 is important to ensure appropriate antiretroviral treatment (ART) and epidemiological surveillance. However, serological tests have shown frequent mistyping when applied in the field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. METHODS: Samples from 239 ART-naïve HIV-infected patients from the Bissau HIV Cohort in Guinea-Bissau were selected retrospectively based on the initial HIV typing performed in Bissau, ensuring a broad representation of HIV types. INNO-LIA results were interpreted by the newest software algorithm, and three independent observers read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for confirmation. RESULTS: INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV-2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive samples could be confirmed by the nucleic acid results. Overall, the observers found that the ImmunoComb results differed from the INNO-LIA results, with agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2. The combined kappa-score for agreement between the three observers was 0.955 (z-score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None of these samples had detectable HIV-1 RNA or DNA. CONCLUSIONS: There was accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.

Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.

We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322 controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1 (TCIRG1)) using single and multilocus analyses to determine whether previously described associations with pulmonary tuberculosis (PTB) in Vietnamese and Italians would replicate in African populations. We did not detect any significant single locus or haplotype associations in either sample. We also performed exploratory pairwise interaction analyses using Visualization of Statistical Epistasis Networks (ViSEN), a novel method to detect only interactions among multiple variables, to elucidate possible interaction effects between SNPs and demographic factors. Although we found no strong evidence of marginal effects, there were several significant pairwise interactions that were identified in either the Guinea-Bissau or the Gambian samples, two of which replicated across populations. Our results indicate that the effects of EREG and TCIRG1 variants on PTB susceptibility, to the extent that they exist, are dependent on gene-gene interactions in West African populations as detected with ViSEN. In addition, epistatic effects are likely to be influenced by inter- and intra-population differences in genetic or environmental context and/or the mycobacterial lineages causing disease.

Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients.

OBJECTIVES: In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. METHODS: Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. RESULTS: Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. CONCLUSIONS: New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation.

Decline in overall, smear-negative and HIV-positive TB incidence while smear-positive incidence stays stable in Guinea-Bissau 2004-2011.

OBJECTIVE: To calculate Tuberculosis (TB) incidence rates in Guinea-Bissau over an 8-year period. METHODS: Since 2003, a surveillance system has registered all TB cases in six suburban districts of Bissau. In this population-based prospective follow-up study, 1205 cases of pulmonary TB were identified between January 2004 and December 2011. Incidence rates were calculated using census data from the Bandim Health and Demographic Surveillance System (HDSS). RESULTS: The overall incidence of pulmonary TB was 279 per 100,000 person-years of observation; the male incidence being 385, and the female 191. TB incidence rates increased significantly with age in both sexes, regardless of smear or HIV status. Despite a peak with unknown cause of 352 per 100,000 in 2007, the overall incidence of pulmonary TB declined over the period. The incidence of HIV infected TB cases declined significantly from 108 to 39 per 100,000, while the incidence of smear-positive TB cases remained stable; the overall figure was 188 per 100,000. CONCLUSIONS: Overall incidence of pulmonary TB in Guinea-Bissau has declined from 2004 to 2011. The decline was also seen in the subgroups of smear-negative and HIV-positive TB cases, probably due to antiretroviral treatment. Smear-positive TB incidence remains stable over the period.

A structured 2-week follow-up visit in the cascade of care for TB increases case detection.

Delayed detection in TB due to structural and diagnostic shortcomings is pivotal for disease transmission, morbidity and mortality. We investigated whether an inclusive screening, followed by a structured clinical follow-up (FU) could improve case-finding.Patients were recruited from health centres in Bissau, Guinea-Bissau, and Gondar, Ethiopia. A routine FU was done at Week 2. If persisting symptoms were found, patients were investigated using chest X-ray (CXR) and Xpert® MTB/RIF, followed by a medical consultation. The main outcome were additional TB patients diagnosed by applying the FU strategy.Of 3,571 adults, 3,285 (95%) were examined at Week 2 FU, where 2,491 (72%) were asymptomatic. Screening patients presenting with cough >2 weeks alone contributed to the diagnosis of 93 patients (45% of all patients diagnosed here), whereas a TBscore >3 increased this by 18 (9%); adding a Week 2 FU yielded an additional 94 (46%) patients. Among the 794 (24%) with persisting symptoms, 25 were diagnosed using Xpert and 69 at clinical FU, which constituted 46% (94/205) of the total TB patients diagnosed.A Week 2 FU visit, which can be nested into routine healthcare, increased the diagnosis of TB patients by two-fold and avoids diagnostic gaps in the cascade-of-care..

Stool testing for pulmonary TB diagnosis in adults.

BACKGROUND: Mycobacterium tuberculosis is acid-fast and able to survive in the gastrointestinal tract. Thus, bacteria can be found in stool if sputum is swallowed. In this study, the accuracy of different diagnostic stool methods (microscopy, polymerase chain reaction PCR and culture) among adults with pulmonary TB (PTB) were assessed and compared with sputum culture.METHODS: Embase and PubMed were searched to identify studies with data on stool testing among patients with clinically presumed or microbiologically verified PTB.RESULTS: Thirteen relevant studies were included. A pooled sensitivity of one or more of the three TB identifying methods was 79.1% (95% CI 61.5-92.5). The sensitivity of stool microscopy, PCR and culture was respectively 41.1% (95%CI 24.9-58.2), 89.7% (95% CI 81.4-95.9) and 38.0% (95% CI 26.2-50.6). The heterogeneity of the studies included was high.CONCLUSION: Our review findings indicate that the analysis of stool specimens as part of PTB diagnostics is useful. PCR methods were particularly helpful in detecting a substantial proportion of patients with PTB.

TB-related deaths among adults in Guinea-Bissau.

SETTING: In an urban demographic, high TB burden surveillance site in Guinea-Bissau, most deaths occur at home, and information on cause of death (CoD) is lacking.OBJECTIVE: To examine CoD and the proportion of TB deaths in three groups: among patients examined for TB without a verified diagnosis after diagnostic workup, described as "assumed TB-negative" (aTBneg), among patients with a confirmed diagnosis of TB and in a sample of the background population.DESIGN: Verbal autopsies (VAs) were obtained for registered deaths occurring between 1 January 2010 and 15 June 2016. All deaths among aTBneg and patients with TB, and a sample of deaths in the background population were included.RESULTS: VAs were obtained from 104/112 aTBneg patients, 140/155 patients with TB, and 172/219 from the general population. The leading CoD was TB in respectively 20%, 69% and 9% of the cohorts. HIV/AIDS-related deaths were the most frequent CoD among aTBneg patients (45%) and in the background population (27%), and accounted for 9% of patients with TB.CONCLUSION: TB was shown to be a frequent CoD, not only among patients diagnosed with TB, but also among aTBneg patients and the background population. This indicates a low TB case detection rate.

A self-rated health score predicts severe disease and high mortality in patients with pulmonary TB.

BACKGROUND: Health-related quality of life (HRQoL) in patients with pulmonary TB may be predictive of disease outcome; however, HRQoL instruments are often complicated and unsuitable for use in low-resource settings. A single-item self-rated health (SRH) score may represent a simpler alternative which could be used in clinical decision-making.AIMS: To evaluate internal and external validity of SRH and its correlation with TBscore/TBscoreII in a low-resource setting.METHODS: We used data from our ongoing prospective TB cohort study in Guinea-Bissau. Cohen´s d was used to assess internal validity, and receiver-operating characteristics and mortality statistics to assess external validity. Correlation between SRH and TBscore/TBscoreII was estimated using linear regression.RESULTS: SRH showed satisfactory internal validity and ability to discriminate between fatal cases at high and low scores, although not at middling scores. SRH and TBscore/TBscoreII correlated well at each examination but changes in scores did not, which may be due to ceiling/floor effects and a lag between disease severity and HRQoL.CONCLUSION: SRH shows potential as a quick and simple method to identify patients in need of intensified follow-up during treatment provision. More research is needed to assess its generalisability beyond our setting and to develop models for clinical use of SRH.

Hypertension is associated with increased mortality in patients with tuberculosis in Guinea-Bissau.

OBJECTIVES: Tuberculosis (TB) is associated with a number of non-communicable co-morbidities, which can complicate treatment and impair outcome. The aim of this study was to assess the impact of hypertension on disease severity, treatment outcome and survival in a cohort of patients with TB. METHODS: A retrospective cohort study was conducted in Guinea-Bissau. Patients newly diagnosed with TB between November 2003 and June 2016 were included. Hypertension was defined as blood pressure ≥140/90 mmHg. Disease severity was assessed using the Bandim TBscore. Survival was assessed at the end of treatment and 2 years after treatment initiation. RESULTS: In total, 1544 patients were included in this study. Hypertension was present in 12.8% of patients at inclusion. Patients with hypertension had slightly less severe TB, but were less likely to have a successful treatment outcome and had 64% higher mortality at 2-year follow-up (adjusted hazard ratio 1.64, 95% confidence interval 1.15-2.34). Mortality rates were highest in hypertensive female patients and patients aged ≥ 45 years. CONCLUSION: Patients with high blood pressure at the start of TB treatment had a higher mortality rate at 2-year follow-up. Mortality rates were highest in hypertensive females and patients aged ≥ 45 years.

Historical review of studies on the effect of treating latent tuberculosis.

Tuberculosis Preventive Therapy (TPT) is widely used in particular among high-risk populations such as close contacts and immunosuppressed people mostly in high-income settings. TPT is widely recommended for high-risk populations including HIV-infected and household contacts globally, but is not widely used. Historical trials on risk groups as well as the general population have documented a marked effect on reductions in incidence of active disease among those treated, as well as on prevalence of latent TB infection (LTBI) in populations where massive roll-out of TPT has previously taken place. This review summarizes the results of large historical trials conducted more than 50 years ago among Inuit and African populations as well as risk groups in the USA and Europe exhibiting similarities with current high-burden populations with current limited use of TPT. The trials demonstrated a 27-95% reduction in incidence of active TB among those receiving preventive treatment compared with placebo, with efficacy depending somewhat on length of treatment but mostly on adherence rates. It was possible to achieve satisfactory adherence rates in most of the trial populations and liver toxicity rates were generally low. The historical trials on preventive treatment for LTBI have documented that large-scale TPT is possible and effective even in high-burden populations in high-incidence areas and is therefore a relevant tool to consider in striving to eliminate the TB epidemic.

High coverage of polio immunization program in refugees resettling in Denmark. A cross-sectional study of polio serology in newly arrived refugees.

Objectives: Wild poliovirus (WPV) infection has been eliminated in Europe through mass immunization. Resettling refugees may lack immunity and importing WPV through refugees continues to cause concerns.Method: We performed a cross-sectional study to establish the prevalence of poliovirus immunity in children and adult refugees resettling in Aarhus, Denmark. Immunity was evaluated by antibody response for serotypes 1, 2, and 3.Results: The participants in this study counted a total of 475 children and adult refugees aged between 6 months and 76 years and 59% were males. The survey was conducted between 2014 and 2016. Among the refugees, 72% were from Syria, and the rest from Eritrea, Congo, Lebanon, Somalia, Afghanistan, Iran, Iraq, Ethiopia, and Columbia. In the cohort, 27 lacked antibodies against a least one serotype. None of the participants lacked antibodies against all three polio types. Originating from The Horn of Africa, age between 20 and 30 and male gender was associated with lack of immunity.Conclusion: The study found a complete WPV immunity in 94% of recently resettled refugees in Denmark. This study demonstrates a high coverage of the polio immunization program. However, ensuring poliovirus immunity among refugees remains a priority until polio has been eradicated worldwide.

A clinical case of tuberculosis with transient constrictive pericarditis and perimyocarditis.

Tuberculous pericarditis is a rare diagnosis seen among as few as 1% of tuberculosis (TB) patients in developed countries. We present a case of a 60-year-old male suffering from a transient constrictive pericarditis and subclinical involvement of the myocardium in a clinical case of tuberculous pericarditis with corresponding improvement after the initiation of anti-tuberculous treatment. We suggest monitoring of myocardial function using global longitudinal strain by myocardial speckle tracking strain analysis as supplement to routine left ventricular ejection fraction to assess clinical improvement in patients at risk of developing constrictive pericarditis. LEARNING POINTS: Tuberculous pericarditis is rare and a diagnostic challenge in low-incidence countries.Patients with tuberculosis and involvement of the heart are at high risk of developing constrictive pericarditis.Novel imaging techniques, such as estimation of global longitudinal strain using myocardial speckle tracking analysis, may be useful in assessing cardiac involvement in tuberculosis patients.

Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis.

OBJECTIVE: To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB).DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded.RESULTS: In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, P < 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore >6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality.CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.

Long-term effects of smallpox vaccination on expression of the HIV-1 co-receptor CCR5 in women.

BACKGROUND: Smallpox vaccinations were stopped globally in 1980. Recent studies have shown that in women, being smallpox vaccinated was associated with a reduced risk of HIV infection compared with not being smallpox vaccinated. At the initial infection, HIV-1 most often uses CCR5 as a co-receptor to infect the T-lymphocytes. We therefore investigated whether smallpox vaccination is associated with a down-regulation of CCR5 on the surface of peripheral T-lymphocytes in healthy women in Guinea-Bissau. METHODS: We included HIV seronegative women from Bissau, Guinea-Bissau, born before 1974, with and without a smallpox vaccination scar. Blood samples were stabilised in a TransFix buffer solution and stained for flow cytometry according to a T-cell maturation profile. RESULTS: Ninety-seven women were included in the study; 52 with a smallpox vaccination scar and 45 without a scar. No association between smallpox vaccination scar and CCR5 expression was found in any T-lymphocyte subtype. CONCLUSION: Among HIV seronegative women, being smallpox vaccinated more than 40 years ago was not associated with a down-regulation of CCR5 receptors on the surface of peripheral T-lymphocytes.

Low prevalence of malnourishment among household contacts of patients with tuberculosis in Guinea-Bissau.

SETTING: An urban demographic surveillance site in Bissau, the capital of Guinea-Bissau, West Africa.BACKGROUND We hypothesised that if previous malnutrition plays a part in acquiring active tuberculosis (TB) disease, households of TB cases would have a higher prevalence of malnutrition than those of healthy controls. DESIGN: A cross-sectional study comparing nutritional and socio-economic status of all newly diagnosed patients with TB in 2014 with household contacts (persons residing in the household of TB cases) and random controls. Exclusion criteria were extra-pulmonary TB, age <15 years and pregnancy. RESULTS: Prevalence of malnutrition was 5% in household contacts and healthy controls, and 51% in patients with TB. Patients with TB had 22% (95%CI 19-25) lower body weight, 22% (95%CI 20-25) lower body mass index and 22% (95%CI 19-24) lower mid-upper arm circumference than healthy controls (P < 0.001); household contacts and healthy controls were comparable for all measures. The socio-economic status of households with TB cases was lower. CONCLUSIONS: We did not find a higher prevalence of malnourishment in households with TB cases. This finding did not support the hypothesis that malnourishment was an important causative factor for the development of active TB among patients in this study.