The impact of the COVID-19 pandemic on healthcare access and utilisation in South Sudan: a cross-sectional mixed methods study.

BACKGROUND: Indirect effects of the COVID-19 pandemic on communities in fragile and conflict-affected settings may be severe due to reduced access and use of healthcare, as happened during the 2015 Ebola Virus Disease outbreak. Achieving a balance between short-term emergency response and addressing long-term health needs is particularly challenging in fragile and conflict-affected settings such as South Sudan, given the already significant barriers to accessing healthcare for the population. This study sought to characterise the effect of COVID-19 on healthcare access and South Sudan's healthcare response. This can inform efforts to mitigate the potential impacts of COVID-19 or other epidemiological threats, and contribute to understanding how these may be balanced for greater health system resilience in fragile contexts. METHODS: We conducted a mixed methods study in three of South Sudan's states, combining data from a cross-sectional quantitative household survey with qualitative interviews and Focus Group Discussions. RESULTS: Even though some fears related to COVID-19 were reported, we found these did not greatly dissuade people from seeking care and do not yield significant consequences for health system programming in South Sudan. The pillars of the response focused on risk communication and community engagement were effective in reaching communities through different channels. Respondents and participants reported behaviour changes that were in line with public health advice. We also found that the implementation of COVID-19 response activities sometimes created frictions between the national government and international health actors, and that COVID-19 caused a greater reliance on, and increased responsibility for, international donors for health planning. CONCLUSIONS: Given the fact that global priorities on COVID-19 are greatly shifting, power dynamics between international health agencies and the national government may be useful to consider in further COVID-19 planning, particularly for the vaccine roll-out. South Sudan must now navigate a period of transition where COVID-19 vaccine roll-out continues and other domestic health burdens are re-prioritised.

Increasing TB/HIV Case Notification through an Active Case-Finding Approach among Rural and Mining Communities in Northwest Tanzania.

While Tanzania is among the high TB burden countries to reach the WHO's End TB 2030 milestones, 41% of the people estimated to have had TB in 2020 were not diagnosed and notified. As part of the response to close the TB treatment coverage gap, SHDEPHA+ Kahama conducted a TB REACH active case-finding (ACF) intervention among rural and mining communities in Northwest Tanzania to increase TB/HIV case notification from July 2017 to June 2020. The intervention successfully linked marginalized mining communities with integrated TB/HIV screening, diagnostic, and referral services, screening 144,707 people for TB of whom 24,200 were tested for TB and 4,478 were tested for HIV, diagnosing 1,499 people with TB and 1,273 people with HIV (including at least 154 people with TB/HIV coinfection). The intervention revealed that community-based ACF can ensure high rates of linkage to care among hard-to-reach populations for TB. Providing integrated TB and HIV screening and diagnostic services during evening hours (Moonlight Events) in and around mining settlements can yield a large number of people with undiagnosed TB and HIV. For TB, this is true not only amongst miners but also FSW living in the same communities, who appear to be at similar or equally high risk of infection. Local NGOs can help to bridge the TB treatment coverage gap and to improve TB and HIV health outcomes by linking these marginalized groups with public sector services. Capturing the number of referrals arriving at CTCs is an important next step to identify how well the integrated TB/HIV outreach services operate and how they can be strengthened.

Correlates of observing and willingness to report stigma towards HIV clients by (TB) health workers in Africa.

SETTING: Health care facilities in Kenya, Tanzania and Namibia. OBJECTIVE: To study the factors associated with the observation of and willingness to report stigmatising behaviour towards persons living with the human immunodeficiency virus (HIV) among health care workers (HCWs). DESIGN: Mixed-effect logistic regression analyses of 9516 HCW interviews, including those of 4062 (43%) TB workers carried out as part of the Service Provision Assessments (SPAs) between 2006 and 2010. RESULT: Discrimination (i.e., enacted stigma) was observed by respectively 1042 (60%), 384 (40%) and 907 (69%) TB workers in Kenya, Namibia and Tanzania, similar to the trend observed among all HCWs. Observations of discrimination were clustered at facility level in Kenya, and mapping of facility-level discrimination suggested geographic clustering. HCWs were more likely to observe discrimination in facilities without regular supportive supervision (adjusted OR [aOR] 2.33, 95%CI 1.09-4.96). No HCW characteristics were found to predict intention to report. Training in patients' rights and in confidentiality predisposed HCWs to recognise discrimination (aOR 2.51, 95%CI 1.19-5.28) and the willingness to report it (aOR 2.23, 95%CI 1.11-4.47). Exposure to training in TB infection control (IC) was associated with greater willingness to report discrimination (aOR 2.13, 95%CI 1.03-4.39). CONCLUSION: Supervision and exposure to training in patient's rights and confidentiality improved HCWs' understanding and advocacy of dignified and respectful TB-HIV care. All HCWs are equally likely to be allies, agents of change and amplifiers of an anti-stigma message, and broad engagement is required. Innovative approaches to reduce discrimination-while ensuring proper IC-should be explored.

Point-of-care management of urogenital Chlamydia trachomatis via Gram-stained smear analysis in male high-risk patients. Diagnostic accuracy and cost-effectiveness before and after changing the screening indication at the STI Clinic in Amsterdam.

OBJECTIVES: To measure the effect of changing the point-of-care (POC) testing algorithm of urogenital chlamydia for all male high-risk patients to those with only symptoms with respect to: diagnostic accuracy, loss to follow-up, correctly managed consultations and costs. METHODS: Retrospective comparison of the diagnostic accuracy and cost-effectiveness of Gram-stained urethral smear analysis for the POC management of urogenital Chlamydia trachomatis infections. Between 2008 and 2009 Gram-stained urethral smear analysis was offered to all men irrespective of symptoms; between 2010 and 2011 only to those with symptoms. The Aptima CT assay was the reference diagnostic test. RESULTS: The number of examined Gram-stained smears in the two periods was respectively 7185 (2008-2009 period) and 18,852 (2010-2011 period). The sensitivity of the Gram stain analysis was respectively 83.8% (95% CI 81.2% to 86.1%) and 91.0% (95% CI 89.5% to 92.3%) (p<0.001). The specificity was respectively 74.1% (95% CI 73.0% to 75.2%) and 53.1% (95% CI 51.8% to 54.4%) (p<0.001). The positive predictive value was low in both periods, respectively 31.7% (95% CI 29.8% to 33.6%) and 35.6% (95% CI 34.1% to 37.1%) (p=0.002), whereas the negative predictive value was high, respectively 97.0% (95% CI 96.4% to 97.4%) and 95.4% (95% CI 94.6% to 96.1%) (p=0.002). The loss to follow-up rate between 2008-2009 and 2010-2011 was, respectively, 1.8% (95% CI 1.0% to 2.9%) vs 2.3% (95% CI 1.7% to 3.0%) (p=0.36). There was a small difference in overtreatment, 68.0% (95% CI 66.0% to 69.8%) vs 64.1% (95% CI 62.6% to 65.5%) (p=0.001). The cost per correctly managed consultation was 14.3% lower in the 2010-2011 period (€94.31 vs €80.82). The percentage of delayed treated infections was significantly lower in the 2008-2009 period (10.5%) compared with the 2010-2011 period (22.8%) (p<0.001). CONCLUSIONS: With a high sensitivity in male high-risk patients, the Gram-stained urethral smear is a useful POC test to detect urogenital C. trachomatis. When offered only to men with urogenital symptoms the specificity decreases but the cost per correctly managed consultation is reduced with 14.3% without a significant difference in loss to follow-up but with a significantly higher rate of delayed treatment.

Comparison of two Gram stain point-of-care systems for urogenital gonorrhoea among high-risk patients: diagnostic accuracy and cost-effectiveness before and after changing the screening algorithm at an STI clinic in Amsterdam.

OBJECTIVES: To compare point-of-care (POC) systems in two different periods: (1) before 2010 when all high-risk patients were offered POC management for urogenital gonorrhoea by Gram stain examination; and (2) after 2010 when only those with symptoms were offered Gram stain examination. METHODS: Retrospective comparison of a Gram stain POC system to all high-risk patients (2008-2009) with only those with urogenital symptoms (2010-2011) on diagnostic accuracy, loss to follow-up, presumptively and correctly treated infections and diagnostic costs. Culture was the reference diagnostic method. RESULTS: In men the sensitivity of the Gram stain was 95.9% (95% CI 93.1% to 97.8%) in 2008-2009 and 95.4% (95% CI 93.7% to 96.8%) in 2010-2011, and in women the sensitivity was 32.0% (95% CI 19.5% to 46.7%) and 23.1% (95% CI 16.1% to 31.3%), respectively. In both periods the overall specificity was high (99.9% (95% CI 99.8% to 100%) and 99.8% (95% CI 99.7% to 99.9%), respectively). The positive predictive value (PPV) and negative predictive value (NPV) before and after 2010 were also high: PPV 97.0% (95% CI 94.5% to 98.5%) and 97.7% (95% CI 96.3% to 98.6%), respectively; NPV 99.6% (95% CI 99.4% to 99.7%) and 98.8% (95% CI 98.5% to 99.0%), respectively. There were no differences between the two time periods in loss to follow-up (7.1% vs 7.0%). Offering Gram stains only to symptomatic high-risk patients as opposed to all high-risk patients saved €2.34 per correctly managed consultation (a reduction of 7.7%). CONCLUSIONS: The sensitivity of the Gram stain is high in men but low in women. When offered only to high-risk patients with urogenital symptoms, the cost per correctly managed consultation is reduced by 7.7% without a significant difference in accuracy and loss to follow-up.

No added value of performing Ziehl-Neelsen on auramine-positive samples for tuberculosis diagnostics.

SETTING: Regional Laboratory for Tuberculosis, Amsterdam, The Netherlands. BACKGROUND: There is a push to switch from Ziehl-Neelsen (ZN) to auramine microscopy. Despite World Health Organization guidelines that one staining method is sufficient, in some countries national guidelines prescribe that auramine-positive samples should be confirmed by ZN. OBJECTIVE: To investigate the added value of confirming auramine-positive samples using ZN. DESIGN: Using diagnostic data from 10 276 respiratory samples collected from 5525 patients tested for tuberculosis (TB) at the Municipal Health Service of Amsterdam between May 2006 and October 2011, we determined the diagnostic accuracy of auramine alone and of confirmation of auramine-positive samples using ZN. RESULTS: Of 141 M. tuberculosis complex-positive samples detected using auramine on which ZN was performed, 32 (22.7%) were ZN-negative. A similar percentage (6/25, 24.0%) of negatives was found for samples containing non-tuberculous mycobacteria (NTM) species, thus making it impossible to distinguish between TB and NTM on the basis of ZN results. CONCLUSIONS: A positive auramine result followed by a negative ZN result could not be used to exclude TB or to indicate the presence of NTM species. Confirming auramine-positive samples using ZN in this setting thus provided no clinically informative information and was a waste of resources.

[Differences in European influenza pandemic preparedness plans, how important are they and what are the underlying reasons?]. / Wie gross sind die Differenzen zwischen den europäischen Pandemieplänen, sind sie relevant und woher stammen sie?

The coordination of influenza pandemic preparedness planning within Europe is especially important for Germany with 10 out of 16 Länder (regions) bordering neighbouring countries. The language barrier presents only one of the challenges to overcome. Creating a European early warning system by linking national surveillance structures and the development of a communication network are important initial achievements. Several instruments have been designed and the European Centre for Disease Prevention and Control has already played a major role in the coordination of this process. It has also led the assessment of preparedness and planning by Member States. The speed of the European Member States in preparing for and the foci they have chosen when dealing with an influenza outbreak are heterogeneous. The simultaneous analysis presented here from European, national and regional points of view aims to identify both opportunities and risks of this diversity in Europe for coping with a new pandemic. Regional and local initiatives for cross-border measures and crisis management will play a central role in achieving successful influenza pandemic preparedness in Europe.

Pneumococcal vaccines for preventing otitis media.

BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Long term effects of recurrent episodes of otitis media, rapid emergence of drug resistant bacteria associated with AOM worldwide and huge estimated direct and indirect annual costs associated with otitis media have emphasized the need for an effective vaccination program to prevent episodes of AOM. OBJECTIVES: The object of this review was to assess the effect of pneumococcal vaccination in preventing AOM in children up to 12 years of age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 2, 2003) which contains the Cochrane Acute Respiratory Infection Group's specialised register (30th June 2003), MEDLINE (January 1966 to June 2003), EMBASE (January 1990 to June 2003) and reference lists of all studies and review articles retrieved. We also contacted two vaccine manufacturers and first or corresponding authors of some of the included studies. SELECTION CRITERIA: Randomised controlled clinical trials of pneumococcal vaccination with prevention of AOM as outcome in children aged 12 years or younger and a follow-up of at least six months after vaccination. DATA COLLECTION AND ANALYSIS: Five reviewers independently assessed trial quality and two reviewers extracted data. Two study authors were contacted. MAIN RESULTS: Eight trials on 8-to 14-valent pneumococcal polysaccharide vaccine (PPV) and four trials on 7-to 9-valent pneumococcal conjugate vaccine (PCV) were included. The highest efficacy of PPV was found in children aged 24 months and older: the rate ratio was 0.779 [95% CI: 0.625-0.970]. PPV has little effect on the prevention of AOM in children without documented prior episodes of AOM and only a moderate effect in the group of children with documented AOM episodes prior to vaccination. Pooled results of the four PCV trials in infants vaccinated as early as two months of age and toddlers attending daycare and toddlers with recurrent AOM showed only a small effect on prevention of AOM (rate ratio 0.921; 95% CI: 0.894-0.950). REVIEWER'S CONCLUSIONS: Based on the currently available results of the effectiveness of pneumococcal vaccination for the prevention of AOM, a large scale use of pneumococcal polysaccharide and conjugate vaccination for this specific indication is not yet recommended. So far, pneumococcal conjugate vaccinations are not indicated in the management of recurrent AOM in toddlers and older children. The results of currently ongoing trials of 9- and 11-valent conjugate vaccines should provide more information as to whether pneumococcal vaccines are more effective in specific high-risk populations like infants and older children with recurrent AOM or immunodeficiency.

The effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion at 7 and 24 months of age.

OBJECTIVE: To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect. METHODS: Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled double-blind trial to evaluate the efficacy of pneumococcal conjugate vaccination against acute otitis media. Data on the vaccination effect against otitis media with effusion were obtained by means of symptom interview and pneumatic otoscopy during pre-scheduled follow-up visits at the age of 7 and 24 months. Two endpoint definitions were considered: otitis media/tube (otitis media or tympanostomy tube in situ (OM/T)) as the primary endpoint and otitis media with effusion as the secondary endpoint. No evidence was found of an age-dependent association with vaccination effect. Therefore, the final marginal logistic regression analyses were performed on the combined data from the two follow-up visits. RESULTS: The risk of otitis media tended to be lower in the pneumococcal vaccine group. The odds ratio for otitis media/tube was 0.94 (95% confidence interval 0.77-1.14) and the odds ratio for otitis media with effusion was 0.90 (95% confidence interval 0.69-1.19). Presence of older siblings increased the risk of otitis media/tube and otitis media with effusion at 7 months of age. In addition, it appeared that children without older siblings and attending day-care at 24 months of age tended to benefit more from the pneumococcal conjugate vaccine. In this subgroup, the odds ratio for otitis media/tube was 0.81 (95% confidence interval 0.55-1.20) and for otitis media with effusion the odds ratio was 0.43 (95% confidence interval 0.22-0.86). CONCLUSION: The effect of pneumococcal conjugate vaccination on the risk of otitis media with effusion was concordant with the efficacy seen against acute otitis media, although not distinguishable from no effect in the overall analysis. In children without older siblings, vaccination appeared to reduce the point prevalence of otitis media with effusion; this effect was not apparent in children with older siblings.

Pneumococcal vaccines for preventing otitis media.

BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Long term effects of recurrent episodes of otitis media, rapid emergence of drug resistant bacteria associated with AOM worldwide and huge estimated direct and indirect annual costs associated with otitis media have emphasized the need for an effective vaccination program to prevent episodes of AOM. OBJECTIVES: The object of this review was to assess the effect of pneumococcal vaccination in preventing AOM in children up to 12 years of age. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infection Group specialised register (last update, 26th April 2001), the Cochrane Library (Issue 4, 2000), MEDLINE (January 1966-August 2000) and reference list of all studies and review articles retrieved. We also contacted two vaccine manufacturers and first or corresponding authors of some included studies. SELECTION CRITERIA: Randomised controlled clinical trials of pneumococcal vaccination with prevention of AOM as outcome in children aged 12 years or younger and a follow-up of at least six months. DATA COLLECTION AND ANALYSIS: Five reviewers independently assessed trial quality and two reviewers extracted data. Two study authors were contacted. MAIN RESULTS: Eight trials on pneumococcal polysaccharide vaccine (PPV) and two trials on pneumococcal conjugate vaccine (PCV) were included. The highest efficacy of PPV was found in children aged 24 months and older: the rate ratio after adjustment for study was 0.833 [95%CI: 0.625-0.970]. The PPV has little effect on the prevention of AOM in children without documented prior episodes of AOM and only a moderate effect in the group of children with documented AOM episodes prior to vaccination. The results of the two PCV trials in healthy infants, which followed children from the age of two months until two years of age, could not be pooled because of lack of data. Both studies showed that the risk of recurrent disease decreased with 9% in the group of children receiving the PCV together with other childhood vaccinations at 2,4,6 and 14 months of age: Study Black et al 2000 : risk ratio=0.91[95%CI:0.86-0.96]; Study Eskola et al 2001: risk ratio=0.90 [95%CI:0.73-1.12]. REVIEWER'S CONCLUSIONS: Based on the currently available results of the effectiveness of pneumococcal vaccination for the prevention of AOM, a large scale use of pneumococcal vaccination for this indication is not recommended. The results of currently ongoing trials could provide more information whether pneumococcal vaccines are effective in specific high-risk (otitis-prone) populations.

A comprehensive model for the aetiology of otitis media with effusion.

Otitis media with effusion is highly prevalent among young children. Adverse effects of this disorder are mainly restricted to the group of children with a history of recurrent or persistent otitis media with effusion. Early identification, assessment and intervention might prevent these adverse effects. Up to now it is not possible to distinguish these children from those with transient otitis media with effusion. This article presents a comprehensive model for the aetiology of otitis media with effusion. Eustachian tube functioning and the immunological response to environmental pathogens are the two core elements. This model can be used to formulate specific hypotheses about the interaction of several factors that may lead to the early identification of children who are likely to develop persistent or recurrent otitis media with effusion.

Colonization with mutans streptococci and lactobacilli and the caries experience of children after the age of five.

Some authors suggest that there is a "window of infectivity" for mutans streptococci (MS) at an early age, after which colonization is not likely to occur. Moreover, children with low or non-detectable levels of MS at an early age are at lower risk for caries. It was our aim to study caries experience and colonization with MS and lactobacilli in a group of children at 11 years of age who had been documented to have been MS-free until 5 years of age. For this group, the mfs and MFS values at 11 years of age were found to be 1.12+/-2.81 and 0.44+/-0.88, respectively. These values are much lower than those of a control group of 11-year-old children who had always been MS-positive since the age of 2, being 3.10+/-3.43 and 1.20+/-1.91, respectively. Of the 30 children without detectable MS up to the age of 5, 22 had acquired MS at 11 years of age, but their MS counts were significantly lower than those of the control group. No correlation was observed between the levels of MS of the children and the mothers. In children at 11 years of age, no differences were found in the numbers of lactobacilli and sugar intakes per week between the children MS-free and the children MS-colonized at 5 years of age. The present study indicates that the acquisition of MS is still possible after the so-called "window of infectivity" and that a delayed acquisition of MS may reduce the caries experience in the primary and permanent dentition at a later age.

[The new fight against mutant streptococci]. / De nieuwe strijd tegen mutans streptokokken.

Mutans streptococci are an important factor in the aetiology of dental caries. New ways of combating these bacteria have become available with the development of molecular biological techniques. One of these strategies involves the genetic modification of mutans streptococci to develop less cariogenic mutants. Acid production and the production of intracellular polysaccharides have been eliminated. But it is not clear yet whether these less cariogenic mutant strains are able to replace the normal mutans streptococci in dental plaque. Immunization is another possibility to suppress mutans streptococci. Antibodies against proteins involved in adherence of mutans streptococci have been raised by active immunization. It is also possible to raise antibodies in cow serum and milk, in eggs of chickens and even in tobacco plants. After isolation, these antibodies are to be applied topically. In the future, these new strategies may prevent or reduce caries. However, further research is necessary to resolve the obstacles on the way to commercial application.

Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora.

In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (GF) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels (mean +/- SEM) of 5.3 +/- 0.3 and 6.7 +/- 0.7 mumole/g Hb, respectively. After 2-NF administration, the adduct levels were 0.022 +/- 0.003 and 0.043 +/- 0.010 mumole/g Hb, respectively. In the GF rats, an adduct level of 0.57 +/- 0.09 was determined after 2-AF administration and no adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rat in vivo.

Solid-phase extraction and gas chromatographic-mass spectrometric determination after hydrolysis of 2-aminofluorene haemoglobin adducts in blood of rats.

2-Nitrofluorene is an environmental pollutant that binds covalently to haemoglobin after nitroreduction and successive N-hydroxylation. these haemoglobin adducts can be cleaved in vitro by mild base-catalysed hydrolysis. For the enrichment of arylamines from the aqueous hydrolysate, an extraction procedure with an organic solvent is widely used. Because of the formation of a thick emulsion layer between the aqueous and organic solvent layers, the extraction is laborious and inefficient. The use of Amberlite XAD2 provides a simple extraction procedure yielding a recovery of ca. 70%. Calibration curves in haemoglobin solution were prepared with a correlation coefficient of 0.998 (n = 12). The inter-day coefficient of variation amounted to 14%.