Optimal symptom combinations to aid COVID-19 case identification: Analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Optimal symptom combinations to aid COVID-19 case identification: analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Tropheryma whipplei in children with diarrhoea in rural Ghana.

Tropheryma whipplei has been hypothesized to be able to cause diarrhoea, but data from young children are scarce. In this hospital-based case-control study 534 stool samples of children aged between 2 months and 15 years from rural Ghana were analysed for the presence of T. whipplei. Overall stool prevalence of T. whipplei was high (27.5%). Although there was no difference in T. whipplei carriage overall between cases and controls, cases aged between 0 and 12 months carried T. whipplei in their stool twice as often as controls without diarrhoea. The results from this study may support the hypothesis that T. whipplei can cause diarrhoea in first-time infection.

Group B Streptococci serotype distribution in pregnant women in Ghana: assessment of potential coverage through future vaccines.

OBJECTIVE: Group B streptococcal (GBS) colonization of pregnant women can lead to subsequent infection of the new-born and potentially fatal invasive disease. Data on GBS colonization prevalence and serotype distribution from Africa are scarce, although GBS-related infections are estimated to contribute substantially to infant mortality. In recent years, GBS vaccine candidates provided promising results in phase I and II clinical trials. We aimed to assess the prevalence and serotype distribution of GBS in Ghana since this knowledge is a prerequisite for future evaluation of vaccine trials. METHODS: This double-centre study was conducted in one rural and one urban hospital in central Ghana, West Africa. Women in late pregnancy (≥35 weeks of gestation) attending the antenatal care clinic (ANC) provided recto-vaginal swabs for GBS testing. GBS isolates were analysed for serotype and antibiotic susceptibility. GBS-positive women were treated with intrapartum antibiotic prophylaxis (IAP) according to current guidelines of the Center for Disease Control and Prevention (CDC). RESULTS: In total, 519 women were recruited at both study sites, recto-vaginal swabs were taken from 509. The overall prevalence of GBS was 19.1% (18.1% in rural Pramso and 23.1% in urban Kumasi, restrospectively). Capsular polysaccharide serotype (CPS) Ia accounted for the most frequent serotype beyond all isolates (28.1%), followed by serotype V (27.1%) and III (21.9%). No resistance to Penicillin was found, resistances to second line antibiotics clindamycin and erythromycin were 3.1% and 1%, respectively. DISCUSSION: Group B Streptococcus serotype distribution in Ghana is similar to that worldwide, but variations in prevalence of certain serotypes between the urban and rural study site were high. Antibiotic resistance of GBS strains was surprisingly low in this study.

Infectious diseases among travellers and migrants in Europe, EuroTravNet 2010.

To investigate trends in travel-associated morbidity with particular emphasis on emerging infections with the potential for introduction into Europe, diagnoses of 7,408 returning travellers presenting to 16 EuroTravNet sites in 2010 were compared with 2008 and 2009. A significant increase in reported Plasmodium falciparum malaria (n=361 (6% of all travel-related morbidity) vs. n=254 (4%) and 260 (5%); p<0.001), P. vivax malaria (n=51 (1%) vs. n=31 (0.5%) and 38 (1%); p=0.027) and dengue fever (n=299 (5%) vs. n=127 (2%) and 127 (2%); p<0.001) was observed. Giardia lamblia was identified in 16% of patients with acute diarrhoea, with no significant annual variation. The proportion of acute diarrhoea due to Campylobacter increased from 7% in 2008 to 12% in 2010 (p=0.001). We recorded 121 patients with pulmonary tuberculosis in 2010, a threefold increase in the proportionate morbidity from 2008 to 2010. In 2010, 60 (0.8%) cases of chronic Chagas disease, 151 (2%) cases of schistosomiasis and 112 (2%) cases of cutaneous larva migrans were reported. Illness patterns in sentinel travellers, captured by EuroTravnet, continue to highlight the potential role of travellers in the emergence of infectious diseases of public health concern in Europe and the relevance of offering medical travel advice and enforcing specific and adequate prophylaxis.

Pulmonary infection with rapidly growing mycobacteria in a singer with achalasia: a case report.

We report the case of a 37-year-old male patient with prolonged pneumonia and achalasia. Culture and molecular genetic typing identified Mycobacterium abscessus as causative agent. Treatment with clarithromycin and minocycline over 8 months gradually resolved the infection. Rapidly growing, non-obligate pathogenic mycobacteria are widespread in the environment. Several cases of pulmonary infections with these mycobacteria in patients with achalasia have been reported, suggesting a causative association. This is the first report of a case with isolation of M. abscessus in this context.

Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria.

Genetic host factors play a substantial role in susceptibility to and severity of malaria, which continues to cause at least one million deaths per year. Recently, members of the toll-like receptor (TLR) family have been shown to be involved in recognition of the etiologic organism Plasmodium falciparum: The glycosylphosphatidylinisitol anchor induces signaling in host cells via TLR-2 and -4, while hemozoin-induced immune activation involves TLR-9. Binding of microbial ligands to the respective TLRs triggers the release of pro-inflammatory cytokines via the TLR/IL-1 receptor (TIR) domain and may contribute to the host response, including pro-inflammatory cytokine induction and malarial fever. In a case-control study among 870 Ghanaian children, we examined the influence of TLR-2, -4, and -9 polymorphisms in susceptibility to severe malaria. TLR-2 variants common in Caucasians and Asians were completely absent. However, we found a new, rare mutation (Leu658Pro), which impairs signaling via TLR-2. We failed to detect any polymorphisms within the TLR-9/interleukin-1 receptor domain. Two frequent TLR-9 promoter polymorphisms did not show a clear association with malaria severity. In contrast, the TLR-4-Asp299Gly variant occurred at a high rate of 17.6% in healthy controls, and was even more frequent in severe malaria patients (24.1%, p<0.05). Likewise, TLR-4-Thr399Ile was seen in 2.4% of healthy children and in 6.2% of patients (p=0.02). TLR-4-Asp299Gly and TLR-4-Thr399Ile conferred an 1.5- and 2.6-fold increased risk of severe malaria, respectively. These findings suggest TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation. However some gray areas also suggest the scope for further improvements.