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Nodding syndrome (NS) is a phenotypic presentation of onchocerciasis-associated epilepsy (OAE). OAE is an important public health problem in areas with high ongoing Onchocerca volvulus transmission. OAE, including NS, is preventable by strengthening onchocerciasis elimination programs. The presence of tau in OAE postmortem brains could be the consequence of neuroinflammation directly or indirectly induced by O . volvulus . Omics research is needed to investigate whether O . volvulus worms contain a neurotropic virus.

In patients with HIV-1 infection who are starting combination antiretroviral therapy (ART), the incidence of immune reconstitution inflammatory syndrome (IRIS) is not well defined. We did a meta-analysis to establish the incidence and lethality of the syndrome in patients with a range of previously diagnosed opportunistic infections, and examined the relation between occurrence and the degree of immunodeficiency. Systematic review identified 54 cohort studies of 13 103 patients starting ART, of whom 1699 developed IRIS. We calculated pooled cumulative incidences with 95% credibility intervals (CrI) by Bayesian methods and did a random-effects metaregression to analyse the relation between CD4 cell count and incidence of IRIS. In patients with previously diagnosed AIDS-defining illnesses, IRIS developed in 37·7% (95% CrI 26·6–49·4) of those with cytomegalovirus retinitis, 19·5% (6·7–44·8) of those with cryptococcal meningitis, 15·7% (9·7–24·5) of those with tuberculosis, 16·7% (2·3–50·7) of those with progressive multifocal leukoencephalopathy, and 6·4% (1·2–24·7) of those with Kaposi's sarcoma, and 12·2% (6·8–19·6) of those with herpes zoster. 16·1% (11·1–22·9) of unselected patients starting ART developed any type of IRIS. 4·5% (2·1–8·6) of patients with any type of IRIS died, 3·2% (0·7–9·2) of those with tuberculosis-associated IRIS died, and 20·8% (5·0–52·7) of those with cryptococcal meningitis died. Metaregression analyses showed that the risk of IRIS is associated with CD4 cell count at the start of ART, with a high risk in patients with fewer than 50 cells per μL. Occurrence of IRIS might therefore be reduced by initiation of ART before immunodeficiency becomes advanced.

Community-directed treatment with ivermectin (CDTi) is used to eliminate onchocerciasis. However, despite 25 years of annual CDTi in Mahenge, Tanzania, the prevalence of onchocerciasis and onchocerciasis-associated epilepsy remained high in certain rural villages. Therefore, in 2019, bi-annual CDTi was introduced in the area. This study assessed the impact of the programme on the incidence of epilepsy in four villages. Door-to-door epilepsy surveys were conducted prior to (2017/18) and after (2021) implementing a bi-annual CDTi program. All household members were screened for epilepsy symptoms using a validated questionnaire, and suspected cases were examined by a medical doctor to confirm/reject the diagnosis of epilepsy. The prevalence and annual incidence of epilepsy, including nodding syndrome, were calculated with 95% Wilson confidence intervals with continuity correction. The latter was also done for CDTi coverage in 2016 and 2021. Precisely 5,444 and 6,598 persons were screened for epilepsy before and after implementing the intervention. The CDTi coverage of the overall population was 82.3% (95%CI: 81.3-83.2%) in 2021 and sustained in both distribution rounds (81.5% and 76.8%). The coverage was particularly high in children and teenagers aged 6 to 18 years (93.2%, 95%CI: 92.1-94.2%). The epilepsy prevalence remained similar: 3.3% (95%CI: 2.9-3.9%) in 2017/18 versus 3.1% (95%CI: 2.7-3.5%) in 2021. However, the incidence of epilepsy declined from 177.6 (95%CI: 121.2-258.5) in 2015-2017 and 2016-2018 to 45.5 (95%CI: 22.2-89.7) in 2019-2021 per 100,000 persons-years. The incidence of probable nodding syndrome varied from 18.4 (95%CI: 4.7-58.5) to 5.1 (95%CI: 0.3-32.8). None of the nine incidence cases of epilepsy for which information on ivermectin intake was available took ivermectin in the year they developed their first seizures. A bi-annual CDTi programme should be implemented in areas with high prevalence of onchocerciasis and epilepsy. High CDTi coverage among children is particularly important to prevent onchocerciasis-associated epilepsy.

The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association. PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome. Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes. Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.

Vaccination is fast becoming a key intervention against the ongoing COVID-19 pandemic. We conducted cross-sectional online surveys to investigate COVID-19 vaccine acceptance across nine Low- and Middle-Income Countries (LMICs; N = 10,183), assuming vaccine effectiveness at 90% and 95%. The prevalence of vaccine acceptance increased from 76.4% (90% effectiveness) to 88.8% (95% effectiveness). Considering a 90% effective vaccine, Malaysia, Thailand, Bangladesh, and five African countries (Democratic Republic of Congo, Benin, Uganda, Malawi, and Mali) had lower acceptance odds compared to Brazil. Individuals who perceived taking the vaccine as important to protect themselves had the highest acceptance odds (aOR 2.49) at 95% effectiveness.Vaccine acceptance was also positively associated with COVID-19 knowledge, worry/fear regarding COVID-19, higher income, younger age, and testing negative for COVID-19. However, chronic disease and female gender reduced the odds for vaccine acceptance. The main reasons underpinning vaccine refusal were fear of side effects (41.2%) and lack of confidence in vaccine effectiveness (15.1%). Further research is needed to identify country-specific reasons for vaccine hesitancy in order to develop mitigation strategies that would ensure high and equitable vaccination coverage across LMICs.

We sought to evaluate the adherence of Vietnamese adults to Coronavirus Disease 2019 (COVID-19) preventive measures, and gain insight into the effects of the epidemic on the daily lives of Vietnamese people. An online questionnaire was administered from March 31 to April 6, 2020. The questionnaire assessed personal preventive behavior (such as physical distancing, wearing a face mask, cough etiquette, regular handwashing and using an alcohol hand sanitizer, body temperature check, and disinfecting mobile phones) and community preventive behavior (such as avoiding meetings, large gatherings, going to the market, avoiding travel in a vehicle/bus with more than 10 persons, and not traveling outside of the local area during the lockdown). A total adherence score was calculated by summing the scores of the 9 personal and the 11 community prevention questions. In total, 2175 respondents completed the questionnaire; mean age: 31.4 ± 10.7; (range: 18-69); 66.9% were women; 54.2% were health professionals and 22.8% were medical students. The mean adherence scores for personal and community preventive measures were 7.23 ± 1.63 (range 1-9) and 9.57 ± 1.12 (range 1-11), respectively. Perceived adaptation of the community to lockdown (Beta (β) = 2.64, 95% Confidence Interval (CI) 1.25-4.03), fears/worries concerning one's health (β = 2.87, 95% CI 0.04-5.70), residing in large cities (β = 19.40, 95% CI 13.78-25.03), access to official COVID-19 information sources (β = 16.45, 95% CI 6.82-26.08), and working in healthcare/medical students (β = 22.53, 95% CI 16.00-29.07) were associated with a higher adherence score to anti-COVID instructions. In conclusion, this study confirmed a high degree of adherence to personal and community preventive behavior among Vietnamese people. Our findings are consistent with the epidemiology of COVID-19 in Vietnam, where there have been few infections and no recorded deaths up to the first week of July 2020.

Nodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found in South Sudan. We aimed to determine whether the latter parasite could be a risk factor for NS in Mahenge. Cases of epilepsy were identified in villages affected by NS in Mahenge, Tanzania, and matched with controls without epilepsy of the same sex, age and village. We examined blood films of cases and controls to identify M. perstans infections. The participants were also asked for sociodemographic and epilepsy information, examined for palpable onchocercal nodules and onchocerciasis-related skin lesions and tested for anti-Onchocerca volvulus antibodies (Ov16 IgG4) by ELISA. Clinical characteristics of cases and controls, O. volvulus exposure status and relevant sociodemographic variables were assessed by a conditional logistic regression model for NS and epilepsy status matched for age, sex and village. A total of 113 epilepsy cases and 132 controls were enrolled, of which, respectively, 56 (49.6%) and 64 (48.5%) were men. The median age in cases and controls was 28.0 (IQR: 22.0-35.0) and 27.0 (IQR: 21.0-33.3) years. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria and 106 (93.8%) had onchocerciasis-associated epilepsy (OAE). M. perstans infection was absent in all participants, while Ov16 seroprevalence was positively associated with probable NS (odds ratio (OR): 5.05, 95%CI: 1.79-14.27) and overall epilepsy (OR: 2.03, 95%CI: 1-07-3.86). Moreover, onchocerciasis-related skin manifestations were only found in the cases (n = 7, p = 0.0040), including persons with probable NS (n = 4, p = 0.0033). Residing longer in the village and having a family history of seizures were positively correlated with Ov16 status and made persons at higher odds for epilepsy, including probable NS. In contrast to O. volvulus, M. perstans is most likely not endemic to Mahenge and, therefore, cannot be a co-factor for NS in the area. Hence, this filaria is unlikely to be the primary and sole causal factor in the development of NS. The main risk factor for NS remains onchocerciasis.

The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important early complication of antiretroviral therapy (ART) in resource-limited settings, especially in patients with tuberculosis. However, there are no consensus case definitions for IRIS or tuberculosis-associated IRIS. Moreover, previously proposed case definitions are not readily applicable in settings where laboratory resources are limited. As a result, existing studies on tuberculosis-associated IRIS have used a variety of non-standardised general case definitions. To rectify this problem, around 100 researchers, including microbiologists, immunologists, clinicians, epidemiologists, clinical trialists, and public-health specialists from 16 countries met in Kampala, Uganda, in November, 2006. At this meeting, consensus case definitions for paradoxical tuberculosis-associated IRIS, ART-associated tuberculosis, and unmasking tuberculosis-associated IRIS were derived, which can be used in high-income and resource-limited settings. It is envisaged that these definitions could be used by clinicians and researchers in a variety of settings to promote standardisation and comparability of data.

Many studies have suggested that onchocerciasis might be associated with epilepsy. Therefore, we did a cohort study to assess the incidence of epilepsy relative to Onchocerca volvulus skin microfilarial density (MFD) measured during childhood and to assess the possibility of a temporal relationship. During onchocerciasis surveys undertaken in 25 villages in Cameroon during 1991–93, we measured MFD in individuals aged 5 years or older. In 2017, we revisited seven of these villages. With a standardised five-item questionnaire, we collected information on the occurrence of epilepsy in 856 individuals who were aged 5–10 years in 1991–93, and had MFD determined during the original surveys. We did multivariable analyses to assess the overall incidence and incidence ratios taking into account age, sex, individual MFD in 1991–93, and onchocerciasis endemicity level in the village. In 2017, we obtained data on the history of epilepsy for 85% (729 of 856) of individuals. Among these individuals, we classified 60 as being suspected cases of epilepsy. The overall incidence of epilepsy was 350 per 100 000 person-years (95% CI 270–450). The adjusted incidence ratio for developing epilepsy was 7·07 (95% CI 0·98–51·26; p=0·0530) in individuals with initial MFD of one to five microfilariae per skin snip (mf per snip), 11·26 (2·73–46·43) in individuals with six to 20 mf per snip, 12·90 (4·40–37·83) in individuals with 21–50 mf per snip, 20·00 (3·71–108·00) in individuals with 51–100 mf per snip, 22·58 (3·21–158·56) in individuals with 101–200 mf per snip, and 28·50 (95% CI 3·84–211·27; p=0·0010) in individuals with more than 200 mf per snip, compared with that of individuals without detectable densities of skin microfilariae. Individual O volvulus MFD in childhood was associated with the risk of either seizures or epilepsy in an onchocerciasis focus in Cameroon. This temporal relationship suggests a potential causal link between onchocerciasis and epilepsy. European Research Council, NSETHIO Project.

Cryptococcal immune reconstitution inflammatory syndrome (IRIS) may present as a clinical worsening or new presentation of cryptococcal disease after initiation of antiretroviral therapy (ART), and is thought to be caused by recovery of cryptococcus-specific immune responses. We have reviewed reports of cryptococcal IRIS and have developed a consensus case definition specifically for paradoxical crytopcoccal IRIS in patients with HIV-1 and known cryptococcal disease before ART, and a separate definition for incident cryptococcosis developed during ART (termed ART-associated cryptococcosis), for which a proportion of cases are likely to be unmasking cryptococcal IRIS. These structured case definitions are intended to aid design of future clinical, epidemiological, and immunopathological studies of cryptococcal IRIS, to standardise diagnostic criteria, and to facilitate comparisons between studies. As for definitions of tuberculosis-associated IRIS, definitions for cryptococcal IRIS should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement.