Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study

Background Skin infections with ulceration are a major health problem in countries of the south Pacifi c region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacifi c islands— Haemophilus ducreyi—as causes of skin ulceration in a yaws-endemic region. Additionally, we identifi ed specifi c signs and symptoms associated with these causative agents of cutaneous ulcers and compared these fi ndings with laboratory-based diagnoses. Methods We did a prospective cohort study of fi ve yaws-endemic villages (total population 3117 people) during a yaws elimination campaign in Papua New Guinea in April, 2013. We enrolled all consenting patients with chronic moist or exudative skin ulcers. We undertook a detailed dermatological assessment, syphilis serology, and PCR on lesional swabs to detect the presence of T pallidum pertenue and H ducreyi. Patients with PCR-confi rmed bacterial infections were included in a comparative analysis of demographics and clinical features. Findings Full outcome data were available for 90 people with skin ulcers. Of these patients, 17 (19%) had negative results in all molecular tests and were therefore excluded from the comparative analyses. A bacterial cause was identifi ed in 73 (81%) participants—either H ducreyi (n=42), T pallidum pertenue (yaws; n=19), or coinfection with both organisms (dual infection; n=12). The demographic characteristics of the patients infected with yaws and with H ducreyi were similar. Skin lesions in patients with yaws and in those with dual infection were larger than those in patients infected with H ducreyi (p=0·071). The lesions in patients with yaws and dual infection were more circular in shape (79% and 67%) than in those infected with H ducreyi (21%; p<0·0001); more likely to have central granulating tissue (90% and 67% vs 14%; p<0·0001); and more likely to have indurated edges (74% and 83% vs 31%; p=0·0003). The prevalence of reactive combined serology (positive T pallidum haemagglutination test and rapid plasmin reagin titre of ≥1:8) was higher in cases of yaws (63%) and dual infections (92%) than in H ducreyi infections (29%; p<0·0001). Interpretation In this yaws-endemic community, H ducreyi is an important and previously unrecognised cause of chronic skin ulceration. Reactive syphilis serology caused by latent yaws can occur in ulcers with the presence of H ducreyi alone. The introduction of PCR for ulcer surveillance could improve the accuracy of diagnosis in countries with yaws eradication campaigns

dhfr and dhps genotype and sulfadoxine-pyrimethamine treatment failure in children with falciparum malaria in the Democratic Republic of Congo

To determine the relationship between mutations in dhfr and dhps and SP treatment failure in Plasmodium falciparum malaria in the Democratic Republic of the Congo (DRC

Sensitivity and specificity of a rapid point-of-care test for active yaws: a comparative study.

BACKGROUND: To eradicate yaws, national control programmes use the Morges strategy (initial mass treatment and biannual resurveys). The resurvey component is designed to actively detect and treat remaining yaws cases and is initiated on the basis of laboratory-supported reactive non-treponemal serology (using the rapid plasma reagin [RPR] test). Unfortunately, the RPR test is available rarely in yaws-endemic areas. We sought to assess a new point-of-care assay-the Dual Path Platform (DPP) syphilis assay, which is based on simultaneous detection of antibodies to treponemal and non-treponemal antigens-for guiding use of antibiotics for yaws eradication. A secondary goal was to ascertain at what timepoint the DPP assay line reverted to negative after treatment. METHODS: 703 children (aged 1-18 years) with suspected clinical yaws living in two remote, yaws-endemic villages in Papua New Guinea were enrolled. Clinical suspicion of yaws was established according to a WHO pictorial guide. We obtained blood samples from all patients. We calculated the sensitivity and specificity of the DPP assay for detection of antibodies to treponemal (T1) and non-treponemal (T2) antigens and compared values against those obtained with standard laboratory tests (the Treponema pallidum haemagglutination assay [TPHA] and the RPR test). We followed up a subsample of children with dually positive serology (T1 and T2) to monitor changes in DPP optical density (using an automatic reader) at 3 and 6 months. This trial is registered with ClinicalTrials.gov, number NCT01841203. FINDINGS: Of 703 participants, 389 (55%) were reactive for TPHA, 305 (43%) for the RPR test, and 287 (41%) for both TPHA and the RPR test. The DPP T1 (treponemal) assay had a sensitivity of 88·4% (95% CI 84·8-91·4) and specificity of 95·2% (92·2-97·3). The DPP T2 (non-treponemal) assay had a sensitivity of 87·9% (83·7-91·3) and specificity of 92·5% (89·4-94·9). In subgroup analyses, sensitivities and specificities did not differ according to type of specimen (plasma vs whole blood). For specimens with an RPR titre of 1:8 or greater, the sensitivity of the DPP T2 assay was 94·1% (95% CI 89·9-96·9). Serological cure (including seroreversion or a fourfold reduction in optical density value) was attained at 6 months in 173 (95%) of 182 children with dual-positive serology. INTERPRETATION: The DPP assay is accurate for identification of antibodies to treponemal and non-treponemal antigens in patients with yaws and avoids the need for laboratory support. A change of diagnostic procedure from the currently implemented RPR test to the simpler DPP assay could ease the implementation of yaws eradication activities. FUNDING: Chembio Diagnostic Systems, Newcrest Mining, and the Papua New Guinea National Department of Health

COVID-19 vaccine hesitancy amongst healthcare workers: An assessment of its magnitude and determinants during the initial phase of national vaccine deployment in Nigeria.

Background: While vaccination plays a critical role in the global response to the COVID-19 pandemic, vaccine rollout remains suboptimal in Nigeria and other Low- and Middle-income countries (LMICs). This study documents the level of hesitancy among health workers (HWs) during the initial COVID-19 vaccine deployment phase in Nigeria and assesses the magnitude and determinants of hesitancy across Nigeria. Methods: A cross sectional study across all States in Nigeria was conducted with over 10,000 HWs interviewed between March and April 2021. Data were cleaned and analyzed with proportions and confidence intervals of hesitancy documented and stratification by HW category. We compared the level of confidence/acceptance to be vaccinated across Nigeria and documented the sources of negative information amongst HWs who refused the vaccine. Findings: Among the 10 184 HWs interviewed, 9 369 [92% (95% CI= 91, 92)] were confident of the COVID-19 vaccines and were already vaccinated at the time of this survey. Compared to HWs who were less than 20 years old, those aged 50 - 59 years were significantly more confident of the COVID-19 vaccines and had been vaccinated (OR=3.8, 95% CI=2.3 - 6.4, p<0.001). Only 858 (8%) of the HWs interviewed reported being hesitant with 57% (479/858) having received negative information, with the commonest source of information from social media (43.4%.). Interpretation: A vast majority of HWs who were offered COVID-19 vaccines as part of the first phase of national vaccine roll out were vaccinated and reported being confident of the COVID-19 vaccines. The reported hesitancy was due mainly to safety issues, and negative information about vaccines from social media. The issues identified remain a significant risk to the success of subsequent phases of the vaccine rollout in Nigeria. Funding: None

Endogenous ouabain and intracellular calcium regulation in vascular smooth muscle

BACKGROUND Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. METHODS A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. RESULTS There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (>=5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (<5%) and 20 to 31 (1.3 to 2.2 million) as non-endemic. Nine districts (0.7 million) had no information. The strong impact of MDA, especially on microfilaria (Mf) prevalence, was noted in sites with repeat surveys. CONCLUSIONS This analytical review of past surveys of LF in Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and locates the population at risk, and can be used to predict the likely impact of MDA and/or vector control. Better targeting of districts by level of prevalence will strengthen the control programme, facilitate monitoring of the disease trend and increase the likelihood of reaching the target of LF elimination by 2020

Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study

Background: Skin infections with ulceration are a major health problem in countries of the south Pacific region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacific islands—Haemophilus ducreyi—as causes of skin ulceration in a yaws-endemic region. Additionally, we identified specific signs and symptoms associated with these causative agents of cutaneous ulcers and compared these findings with laboratory-based diagnoses. Methods: We did a prospective cohort study of five yaws-endemic villages (total population 3117 people) during a yaws elimination campaign in Papua New Guinea in April, 2013. We enrolled all consenting patients with chronic moist or exudative skin ulcers. We undertook a detailed dermatological assessment, syphilis serology, and PCR on lesional swabs to detect the presence of T pallidum pertenue and H ducreyi. Patients with PCR-confirmed bacterial infections were included in a comparative analysis of demographics and clinical features. Findings: Full outcome data were available for 90 people with skin ulcers. Of these patients, 17 (19%) had negative results in all molecular tests and were therefore excluded from the comparative analyses. A bacterial cause was identified in 73 (81%) participants—either H ducreyi (n=42), T pallidum pertenue (yaws; n=19), or coinfection with both organisms (dual infection; n=12). The demographic characteristics of the patients infected with yaws and with H ducreyi were similar. Skin lesions in patients with yaws and in those with dual infection were larger than those in patients infected with H ducreyi (p=0·071). The lesions in patients with yaws and dual infection were more circular in shape (79% and 67%) than in those infected with H ducreyi (21%; p<0·0001); more likely to have central granulating tissue (90% and 67% vs 14%; p<0·0001); and more likely to have indurated edges (74% and 83% vs 31%; p=0·0003). The prevalence of reactive combined serology (positive T pallidum haemagglutination test and rapid plasmin reagin titre of ≥1:8) was higher in cases of yaws (63%) and dual infections (92%) than in H ducreyi infections (29%; p<0·0001). Interpretation: In this yaws-endemic community, H ducreyi is an important and previously unrecognised cause of chronic skin ulceration. Reactive syphilis serology caused by latent yaws can occur in ulcers with the presence of H ducreyi alone. The introduction of PCR for ulcer surveillance could improve the accuracy of diagnosis in countries with yaws eradication campaigns. Funding: Newcrest Mining Company