Dysregulated TGF-ß Production Underlies the Age-Related Vulnerability to Chikungunya Virus.

Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFß production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFß levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFß levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFß secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD.

The performance of the SD BIOLINE Dengue DUO® rapid immunochromatographic test kit for the detection of NS1 antigen, IgM and IgG antibodies during a dengue type 1 epidemic in Jamaica.

BACKGROUND: Dengue is an important mosquito-borne viral infection that affects millions of persons worldwide. Early diagnosis is necessary to effect appropriate management and decrease mortality. Immunochromatographic tests are advantageous in producing dengue test results within 30 min but these results should be sensitive and specific. In this study we evaluated the diagnostic performance of the SD BIOLINE Dengue DUO® rapid immunochromatographic test kit. A panel of 309 dengue and 30 non-dengue single serum samples characterized by using reference enzyme-linked immunosorbent assays (ELISAs) was used. These samples were received in the virology laboratory for routine testing during a dengue type 1 outbreak between October to December, 2012. RESULTS: The overall diagnostic sensitivities of the SD BIOLINE Dengue DUO® rapid testfor IgM, IgG and NSI were 49.3% (95% CI: 41.3-57.4), 39.1% (95% CI: 33.3-45.2) and 90% (95% CI: 82.1-94.7), respectively. The IgM and IgG detection rates were significantly lower than that of the NSI (p < 0.001). However the combination of the IgM detection with NS1 detection or both NS1 and IgG resulted in a significant (p < 0.001) increase in sensitivity to 97.5% (95 % CI: 92.9-99.2) and 98.9% (95 % CI: 96.0-99.7), respectively. These higher sensitivities were achieved without any decrease in specificities. CONCLUSIONS: This study revealed that combining two or more parameters of the SD BIOLINE Dengue DUO® rapid kit significantly improved the sensitivity of diagnosis of dengue virus infection and supports its usefulness in the Jamaican setting.

Magnitude, distribution, and estimated level of underreporting of acute gastroenteritis in Jamaica.

Jamaica is the third largest island in the Caribbean. The epidemiology of acute gastroenteritis (AGE) is important to Jamaica, particularly in the areas of health, tourism, and because of the potential impact on the local workforce and the economy. Data collected by the National Surveillance Unit on the prevalence of AGE transmitted by food are not accurate. To determine the true magnitude, risk factors, and the extent of underreporting of AGE in Jamaica, we conducted a cross-sectional, population-based retrospective survey during the periods of 21 February-7 March and 14-27 June 2009, corresponding to high- and low-AGE season respectively. Of the total 1,920 persons selected randomly by a multistage cluster-sampling process, 1,264 responded (response rate 65.8%). Trained interviewers administered a standardized, validated questionnaire during face-to-face interviews. The overall prevalence of self-reported AGE was 4.0% (95% CI 2.9-5.1) at a rate of 0.5 episodes/per person-year. The highest monthly prevalence of AGE (14.6%) was found among the 1-4 year(s) age-group and the lowest (2.1%) among the 25-44 years age-group. Of the 18 cases (36%) who sought medical care, 11% were hospitalized, 33% were treated with antibiotics, and 66.7% received oral rehydration fluids. Only 2 cases who sought medical care reportedly submitted stool specimens. The mean duration of diarrhoea was 3.1 days, which resulted in a mean loss of 4 productive days, with over half of the cases requiring someone to care for them. The burden of syndromic AGE for 2009 was extrapolated to be 122,711 cases, showing an underreporting factor of 58.9. For every laboratory-confirmed AGE case, it was estimated that 383 more cases were occurring in the population. This research confirms that the prevalence of AGE is underreported in Jamaica and not being adequately detected by the current surveillance system. The components of the integrated surveillance system for AGE in Jamaica, particularly the laboratory aspect, need to be strengthened.

Seroprevalence and Genotype Diversity of Hepatitis C Virus in the Caribbean-A Review.

Hepatitis C (HCV) continues to present a global public health challenge, with no vaccine available for prevention. Despite the availability of direct-acting antivirals (DAAs) to cure HCV, it remains prevalent in many regions including the Caribbean. As efforts are made to eliminate HCV from the region, existing barriers, such as the high cost of DAAs and lack of an established database of HCV cases within the Caribbean, must be addressed. This review seeks to assess epidemiologic trends (seroprevalence and genotypic diversity) of HCV in the Caribbean and identify gaps in surveillance of the disease. The literature for the period 1 January 2005 to October 2022 was reviewed to gather country-specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases using the following keywords: Caribbean, genotype distribution, and general epidemiologic characteristics. The usage pattern of HCV drugs was determined from information obtained from pharmacists across the Caribbean including Jamaica. The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate HCV prevalence. The prevalence of HCV among intravenous drug users (21.9-58.8%), persons living with HIV/AIDS (0.8 to 58.5%), prisoners (32.8-64%), and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83%) was most prevalent followed by genotypes 2 (7.2%) and 3 (2.1%), respectively. Less than 50% of countries in the Caribbean have reliable or well-curated surveillance data on HCV. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (sofosbuvir/velpatasvir) and Harvoni (ledipasvir/sofosbuvir). Some of these drugs are only available in the private sector and are sourced externally whenever needed. While trends point to a potentially higher prevalence of HCV, it will require well-designed random surveys to obtain better estimates of the infection seroprevalence, supported by strong public health laboratory systems. DAAs that are pan-genotypic should translate into treatments that are affordable, accessible, and available to improve cure rates and reduce the HCV burden in the population.

Knowledge, Practice and Attitudes to the Management of Sepsis in Jamaica.

Introduction: Sepsis is a life-threatening dysfunction resulting from the dysregulated host response to infection. The mortality of sepsis in Jamaica remains high amid the proven efficacy of the Surviving Sepsis Guidelines implementation in some countries. Aim of study: To evaluate the inter-relationship of healthcare workers' attitude towards, knowledge of and practice of sepsis management in Jamaica. Material and methods: A survey was done using an anonymous self-administered validated questionnaire to healthcare workers across Jamaica. Questions on knowledge, attitude, and practice of sepsis within private and public hospitals were answered. Results: A total of 616 healthcare workers were eligible for analysis. Most respondents agree that healthcare workers need more training on sepsis (93.7%) and that formal sepsis training modules should be implemented at their hospitals or practice (93.2%). Several signs of sepsis as outlined by qSOFA were correctly identified as such by most respondents (60.6% to 76.4%), with the exception of a low PaCO2 (34.9%), which was correctly identified by a minority of respondents. While a majority (69.3%) were able to correctly define sepsis, only 8.8% of respondents knew the annual sepsis mortality rate. Postgraduate training (p<0.01) and formal sepsis training (p<0.05) were both predictive of high correct knowledge and practice scores. Specialization in Anaesthesia/ Critical Care Medicine (p<0.05) or Emergency Medicine (p<0.05) was predictive of high knowledge scores and Internal Medicine predictive of high practice scores (p<0.01). Conclusions: This study revealed that education for healthcare workers on sepsis and the implementation of SSC is needed in Jamaica.

Patterns of dengue virus IgM and IgG antibodies in suspected cases of dengue in Jamaica, 2003-2006.

The patterns of dengue immunoglobulin (Ig) M and IgG antibodies in patients presenting with dengue-like illnesses during 2003-2006 were investigated using enzyme linked immunosorbent assays (ELISA). The seroprevalence of dengue antibodies, dengue IgM and dengue IgG antibodies were 59.4% (979/1647), 15.4% (254/1647) and 51.1% (841/1647), respectively. A statistically significantly increasing trend in the prevalence of dengue IgG antibodies with age was observed, ranging from 38.4% in patients aged less than 1 year to 90% in those 60 of years and over (p = 0.000; 95% confidence interval (CI) = 0.000-0.002). Conversely the seroprevalence of dengue IgM did not differ significantly with age and no seasonality in the number of cases was observed. The patterns of IgM and IgG antibodies found in the present study are consistent with those found in dengue endemic countries during inter-epidemic periods indicating that an increasing risk of a new dengue outbreak due to the accumulation of susceptible population. Preventive measures should be maintained to control the endemic spread and reduce the risk of outbreaks of dengue in Jamaica. The high seroprevalence rate of dengue IgG antibodies might have implications for the emergence of the more severe forms dengue infection in the Jamaican population.

Evaluation of OneStep Dengue NS1 RapiDip™ InstaTest and OneStep Dengue Fever IgG/IgM RapiCard™ InstaTest during the course of a dengue type 1 epidemic.

We determined the diagnostic performance of the OneStep NS1 and the OneStep IgG/IgM RDT kits against a panel of samples which comprised of 174 dengue positive and 165 dengue negative sera characterized by three reference enzyme-linked immunosorbent assays (ELISAs). The diagnostic sensitivities of the OneStep kits for the detection of individual biomarkers of NS1, IgM and IgG were 90% (95% CI: 82.1-94.7), 32.4% (95% CI: 24.8-40.8) and 44.4% (95% CI: 38.2-50.7), respectively. The combination of the OneStep IgG/IgM kit with the OneStep NS1 kit demonstrated significantly higher sensitivities for the combined NS1/IgM (96.8%; 95% CI: 90.9-99.3) and NS1/IgM/IgG (99.5%; 95% CI: 97.1-99.9)(P<0.001). In conclusion, the OneStep NS1 kit has high sensitivity and specificity and is highly recommended for use. The low sensitivities for IgG (44.4%) and for IgM (32.4%) of the OneStep IgG/IgM kit when used alone suggest it is best used in combination with the OneStep NS1 kit to enhance its overall diagnostic performance.

Leptospirosis and malaria as causes of febrile illness during a dengue epidemic in Jamaica.

BACKGROUND: Epidemics of febrile illnesses are often associated with rainy seasons in the tropics. During 2007-2008 an epidemic of dengue was identified in Jamaica based on serological testing of sera. METHODS: A subset of 3165 of 5400 sera submitted for dengue analysis was tested for Leptospira IgM and malaria IgG using ELISA to determine their role in causing epidemic fever. FINDINGS: Seropositivity for dengue, leptospirosis, and malaria were 38·4 and 6·0 and 6·5%, respectively, indicative of three concurrent epidemics. Mixed exposure to all three diseases was rare (0·1%), as were mixed dengue/malaria (2·4%); dengue/leptospirosis (1·6%), and leptospirosis/malaria (0·03%) exposure. Exposure to dengue and malaria appeared to occur most frequently among children while leptospirosis was more common among adults. CONCLUSION: While serological diagnosis definitively established that dengue was the main cause of the epidemic febrile illness, the data suggested that there may be other causes of fever, which may occur simultaneously. Consequently, leptospirosis and malaria should be considered as causes of fever during epidemics of dengue in endemic areas.

Leptospirosis in suspected cases of dengue in Jamaica, 2002-2007.

Due to overlapping clinical features with other febrile illnesses, the diagnosis of leptospirosis is often overlooked, resulting in delay in treatment and increased mortality. In this study the prevalence of leptospirosis was determined in 590 patients with dengue-like illnesses using the Leptospira IgM dipstick and dengue enzyme-linked immunosorbent assays. Leptospira IgM antibodies were found in 27 (5.0%) patients. Dengue IgM negative (6.9% versus 2.5%, P < 0.05) and dengue IgG positive patients (8.0% versus 3.5%, P < 0.01) were more likely to be leptospira IgM positive. Fever, skin rash, central nervous system and respiratory involvement were the most common presenting features. The presence of arthralgia (P = 0.016), hepatitis (P = 0.000), jaundice (P = 0.003), splenomegaly (P = 0.041) and haematuria (P = 0.029) were associated with leptospirosis. In countries with an endemicity of leptospirosis and dengue it is important that patients with dengue-like illnesses, especially those with no serological evidence of current primary dengue infection, be investigated for leptospirosis.

Seroprevalence of dengue virus antibodies in healthy Jamaicans.

Dengue fever, a mosquito borne viral infection, is endemic to Jamaica. The seroprevalence of dengue IgG and IgM antibodies were determined in 277 healthy Jamaicans by enzyme linked immunosorbent assay (ELISA). The seroprevalence of dengue IgG antibodies was 100% (277/277) while dengue IgM antibodies were found in 3.6% (10/277). A statistically significant association was found between the presence of dengue IgM antibodies and gender (males 10/105, 9.5% vs females 0/172, 0.0%); chi(2) = 17.0, p=0.000.The high seroprevalence rate of dengue IgG antibodies and the presence of dengue IgM in the healthy population are in keeping with the endemicity of the virus in Jamaica. Therefore tests for dengue IgG antibodies are of limited usefulness in Jamaica and can be safely excluded from diagnostic testing as a cost saving measure. Serological diagnosis of current dengue infection should be centred around the dengue IgM tests although the limitations in the predictive values of such tests should also be considered. The results also suggest that the risk of emergence of the more severe forms of dengue, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) in the Jamaican population, due to the presence of enhancing antibodies, is high.

Clinical profile of patients newly diagnosed with human immunodeficiency virus [abstract]

OBJECTIVE: Comprehensive medical examination of newly presenting patients infected with the human immunodeficiency virus (HIV) is important to establish health status and stage disease progession. This study was conducted to determine the clinical and epidemiological characteristics of persons newly diagnosed with HIV presenting a primary care clinic for sexually transmitted infections (STIs). METHODS: A retrospective analysis of the medical records of 125 patients (aged 13 years and over) was undertaken over a 12-month period. All patients were serologically confirmed positive for HIV. Information abstracted included socio-demographic factors, presenting complaints and medical examination findings. The EPI Info 6 software was used for data entry and analysis. RESULTS: Most patients (64 percent) were between 20 and 39 years old (range 14-68 years; M:F= 1:1.4). Five percent were homosexuals/bisexuals. Sixty-five per cent used a condom less than half the time and 10 percent never used condoms. Males were more likely than females to have had multiple sex partners during the last three months (p= 0.01). Initial assessment revealed that 53 percent were asymptomatic, 24 percent symptomatic and 21 percent had AIDS at time of presentation. The most common presentation was generalised by lymphadenopathy (67 percent), which was significantly higher than skin rash (27 percent), oral candidiasis (24 percent), cough (24 percent), weight loss (24 percent), and pallor of mucous membranes (19 percent. p< 0.001). Co-infection with syphilis occurred in five percent of patients. CONCLUSIONS: This study confirms that young people continue to account for the majority of cases of newly diagnosed HIV infection. Heterosexual mode of transmission predominates and women are disapropriately affected. HIV infection should be considered as a differential in patients who have persistent generalized lymphadenopathy and other risk factors. (AU)

The prescribing patterns of doctors in the Kingston Metropolitan region of Jamaica

Rising inflation and the instability of the Jamaican dollar have impacted negatively on the health care of the Jamaican people. Prescription drugs constitute a major component of this health care expenditure. The Generic Act was introduced to promote the dispensing of generic drugs as affordable alternatives to brand-name drugs and seminars targeted doctors to practise rational prescribing of drugs. This study examined the current prescribing patterns of medical doctors with special regard to drug cost and generic prescribing. Six pharmacies were randomly selected from a list from the Pharmaceutical Association of Jamaica, stratified according to three locations. A total of 1020 prescriptions were analyzed for number of items, generics, antibiotics, analgesics, antihypertensives, antidiabetics and whether generic substituiton or repeat was allowed. A self administered questionnaire was also delivered to 170 physicians practising in the Kingston Metropolitan Region who were chosen randomly from a list supplied by the Medical Association of Jamamica. The questionnaire elicited information on demographic charcteristics, factors influencing prescribing decision, prescribing paractice and attitude to generic law and generic prescribing, knowledge of 10 commonly used drugs and sources of information on drug costs. Analysis of prescriptions showed the mean number of drugs prescribed was 1.2 per patient, antibiotics accounted for 30.9 percent of the components of prescriptions, 0.5 percent had substitution and 6 percent were repeat prescriptions. The percentage of drugs prescribed by generic name was 22.1 accounting for 34 per cent of prescriptions. There was no significant difference found by location of pharmacies (chi-squared+2.86, d.f=2, p=0.24). Doctors indicated that drug cost was the third most influential factor determining their prescribing decisions. There were no significant difference found in the prescribing of generics between public and private doctors (chi-squared=2.42, d.f.=2, p>0.05). Most were ignorant about the Generic law as well as the estimated costs of drugs. The respondents agreed that generics were clinically equivalent and more affordable than brand-name drugs. This survey reaffirms the importance of continued medical education being made available and accessible to doctors on relevant health care issues so as to provide better service through more cost effective means. (AU)