[Show abstract][Hide abstract] ABSTRACT: Leprosy, caused by Mycobacterium leprae, is a chronic and progressive granulomatous disease affecting mainly the skin and the peripheral nervous system. If left unrecognized, the infection can lead to permanent nerve damage and disability. The clinical presentation depends on the immune response of the patient and can result in a wide spectrum of symptoms. Leprosy is a rare encounter in Scandinavia but remains endemic in some parts of the world, with some areas reporting an increasing incidence. We performed a retrospective record review of leprosy cases in Denmark from 1980 to 2010 with the purpose of presenting the most common geographical, demographic and clinical findings and to discuss the diagnostic and therapeutic challenges of patients with leprosy.
In total 15 cases were reviewed. The majority (87 %) of leprosy patients in Denmark were born in South- and Southeast Asia, and were presumed to have contracted the infection in their countries of origin. Patients were predominately young males (mean age: 28.6 years). Anaesthetic skin lesion with or without nerve enlargement were the most common clinical presentations (73 %). Immunological leprosy reactions were seen in 40 % of the cases. Diagnoses were based on clinical findings and skin biopsies. Treatment length varied but all patients received multidrug regimens.
Leprosy should be kept in mind when encountering patients with suspicious skin lesions originating from leprosy endemic areas or with history of travel or work in the tropics. Due to the long incubation period with symptoms presenting long after immigration or return, clinicians often do not have the diagnosis in mind. The wide spectrum of symptoms and immunological reactions further complicates the diagnostic process. Treatment of leprosy and the complicated immunological reactions, which frequently accompanies the infection, should be performed in collaboration with a specialist.
[Show abstract][Hide abstract] ABSTRACT: The primary objective of the study was to compare laboratory practices for screening blood donors for syphilis at blood transfusion facilities in Ghana with WHO and The National Blood Service, Ghana (NBSG) recommendations. In addition we estimated the prevalence of syphilis antibodies in blood donors in Ghana.
Full-text · Article · Jan 2016 · International Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Endothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria. This study determined the frequencies of PROCR haplotypes H1–4 and plasma levels of sEPCR in a Tanzanian study population to investigate a possible association with severe malaria.
Study participants were children under 5 years of age admitted at the Korogwe District Hospital (N = 143), and diagnosed as having severe malaria (N = 52; including cerebral malaria N = 17), uncomplicated malaria (N = 24), or an infection other than malaria (N = 67). In addition, blood samples from 71 children living in nearby villages were included. The SNPs defining the haplotypes of PROCR gene were determined by post-PCR ligation detection reaction-fluorescent microsphere assay.
Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001). No difference in the frequency of H3 was found between the non-malaria patients, malaria patients or the village population (P > 0.1). Plasma levels of sEPCR differed between these three groups, with higher sEPCR levels in the village population compared to the hospitalized patients (P < 0.001) and higher levels in malaria patients compared to non-malaria patients (P = 0.001). However, no differences were found in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria.
Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming earlier findings, however, in this Tanzanian population; neither PROCR haplotype nor level of sEPCR was associated with severe malaria, however, larger studies are needed to confirm these findings.
[Show abstract][Hide abstract] ABSTRACT: Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored.
In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene.
We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles.
SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n = 28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3% (n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00-0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic sites which could indicate directional selection through local drug pressure.
Our observations suggest that Pvmdr1 mutations emerged independently on multiple occasions even within the same population. In Sri Lanka population analysis at multiple sites showed evidence of local selection and geographical dispersal of Pvmdr1 mutations between sites.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The association between diabetes mellitus (DM) and tuberculosis (TB) has been established on the basis of cross-sectional studies; however, only a few longitudinal studies have been conducted, with inconsistent results.OBJECTIVE: To study the effect of ethnicity and the presence and duration of DM on the risk of incident TB based on 15 years of follow-up of the entire Danish population.DESIGN AND METHODS: Using Poisson regression analysis, we estimated TB incidence in individuals with DM vs. those without DM by linking nationwide DM and TB registers to the National Civil Register at case level.RESULTS: The TB rate ratio was 1.9 in individuals with DM compared to non-DM individuals, regardless of country of birth, with the exception of African-born individuals (rate ratio 0.5). The risk decreased drastically within the first 2 years after the diagnosis of DM; no association was found with longer durations of DM. The risk also decreased the later the year of DM diagnosis.CONCLUSIONS: The study confirmed DM as a risk factor for TB, except in the case of African-born individuals. Other non-DM risk factors for TB could act as effect-modifiers on the DM-TB association. Implementing earlier DM diagnosis and improving metabolic control may reduce the risk of DM-related TB.
No preview · Article · Oct 2015 · Behaviour and Information Technology
[Show abstract][Hide abstract] ABSTRACT: Background
Haem oxygenase-1 (HO-1) catabolizes haem and has both cytotoxic and cytoprotective effects. Polymorphisms in the promoter of the Haem oxygenase-1 (HMOX1) gene encoding HO-1 have been associated with several diseases including severe malaria. The objective of this study was to determine the allele and genotype frequencies of two single nucleotide polymorphisms; A(−413)T and G(−1135)A, and a (GT)n repeat length polymorphism in the HMOX1 promoter in paediatric malaria patients and controls to determine possible associations with malaria disease severity.
Study participants were Ghanaian children (n=296) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as having uncomplicated malaria (n=101) or severe malaria (n=195; defined as severe anaemia (n=63) or cerebral malaria (n=132)). Furthermore, 287 individuals without a detectable Plasmodium infection or asymptomatic carriers of the parasite were enrolled as controls. Blood samples from participants were extracted for DNA and allele and genotype frequencies were determined with allele-specific PCR, restriction fragment length analysis and microsatellite analysis.
The number of (GT)n repeats in the study participants varied between 21 and 46 with the majority of alleles having lengths of 26 (8.1%), 29/30 (13.2/17.9%) and 39/40 (8.0/13.8%) repeats, and was categorized into short, medium and long repeats. The (−413)T allele was very common (69.8%), while the (−1135)A allele was present in only 17.4% of the Ghanaian population. The G(−1135)A locus was excluded from further analysis after failing the Hardy-Weinberg equilibrium test. No significant differences in allele or genotype distribution of the A(−413)T and (GT)n repeat polymorphisms were found between the controls and the malaria patients, or between the disease groups, for any of the analysed polymorphisms and no associations with malaria severity were found.
These results contribute to the understanding of the role of HMOX1/HO-1. This current study did not find any evidence of association between HMOX1 promoter polymorphisms and malaria susceptibility or severe malaria and hence contradicts previous findings. Further studies are needed to fully elucidate the relationship between HMOX1 polymorphisms and malarial disease.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Few studies have examined the health consequences of living in a household with a person who has been diagnosed with type 2 diabetes (T2D). We assessed the association of sharing a household with a person with diagnosed T2D and risk factors for cardio-metabolic diseases in Uganda, a low-income country.
Ninety households with 437 residents in southwestern Uganda were studied from December 2012 through March 2013. Forty-five of the households had a member with diagnosed T2D (hereafter “diabetic household”), and 45 households had no member with diagnosed T2D (hereafter “nondiabetic household”). We compared glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), hypertension, anthropometry, aerobic capacity, physical activity, nutrition, smoking, and diabetes-related knowledge of people without diagnosed T2D living in diabetic and nondiabetic households.
People living in diabetic households had a significantly higher level of diabetes-related knowledge, lower levels of FPG (5.6 mmol/L vs 6.0 mmol/L), and fewer smoked (1.3% vs 12.9%) than residents of nondiabetic households. HbA1c was significantly lower in people aged 30 years or younger (5.2% vs 5.4%) and in males (5.2% vs 5.4%) living in diabetic households compared to residents of nondiabetic households. No differences were found between the 2 types of households in overweight and obesity, upper-arm fat area, intake of staple foods or cooking oil, or physical activity.
Sharing a household with a person with T2D may have unexpected benefits on the risk factor profile for cardio-metabolic diseases, probably because of improved health behaviors and a closer connection with the health care system. Thus, future studies should consider the household for interventions targeting primary and secondary prevention of T2D.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.
To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).
Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant.
HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 μg/mL (0.75-2.20 μg/mL) and 1.04 μg/mL (0.39-1.71 μg/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13-0.39 μg/mL) and 0.22 μg/mL (0.13-0.34 μg/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05).
After short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk.
[Show abstract][Hide abstract] ABSTRACT: Physical inactivity and low birth weight (LBW) may lead to an increased risk for developing type 2 diabetes. The extent to which LBW individuals may benefit from physical exercise training when compared with those with normal birth weight (NBW) controls is uncertain. We assessed the impact of an outdoor exercise intervention on body composition, insulin secretion and action in young men born with LBW and NBW in rural India. A total of 61 LBW and 56 NBW healthy young men were recruited into the study. The individuals were instructed to perform outdoor bicycle exercise training for 45 min every day. Fasting blood samples, intravenous glucose tolerance tests and bioimpedance body composition assessment were carried out. Physical activity was measured using combined accelerometry and heart rate monitoring during the first and the last week of the intervention. Following the exercise intervention, the LBW group displayed an increase in physical fitness [55.0 ml (O2)/kg min (52.0-58.0)-57.5 ml (O2)/kg min (54.4-60.5)] level and total fat-free mass [10.9% (8.0-13.4)-11.4% (8.0-14.6)], as well as a corresponding decline in the ratio of total fat mass/fat-free mass. In contrast, an increase in total fat percentage as well as total fat mass was observed in the NBW group. After intervention, fasting plasma insulin levels, homoeostasis model assessments (HOMA) of insulin resistance (HOMA-IR) and insulin secretion (HOMA-IS), improved to the same extent in both the groups. In summary, young men born with LBW in rural India benefit metabolically from exercise training to an extent comparable with NBW controls.
Full-text · Article · Dec 2014 · Journal of Developmental Origins of Health and Disease
[Show abstract][Hide abstract] ABSTRACT: Even though Plasmodium vivax has the widest worldwide distribution of the human malaria species and imposes a serious impact on global public health, the investigation of genetic diversity in this species has been limited in comparison to Plasmodium falciparum. Markers of genetic diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations.
The genetic diversity of eight P. vivax populations (n = 543) was investigated by using two microsatellites (MS), m1501 and m3502, chosen because of their seven and eight base-pair (bp) repeat lengths, respectively. These were compared with published data of the same loci from six other P. vivax populations.
In total, 1,440 P. vivax samples from 14 countries on three continents were compared. There was highest heterozygosity within Asian populations, where expected heterozygosity (He) was 0.92-0.98, and alleles with a high repeat number were more common. Pairwise F
ST revealed significant differentiation between most P. vivax populations, with the highest divergence found between Asian and South American populations, yet the majority of the diversity (~89%) was found to exist within rather than between populations.
The MS markers used were informative in both global and local P. vivax population comparisons and their seven and eight bp repeat length facilitated population comparison using data from independent studies. A complex spatial pattern of MS polymorphisms among global P. vivax populations was observed which has potential utility in future epidemiological studies of the P. vivax parasite.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To investigate the diagnostic accuracy of random blood glucose (RBG) on good glycaemic control among patients with diabetes mellitus (DM) in a rural African setting.Methods
Cross-sectional study at St. Francis' Hospital in eastern Zambia. RBG and HbA1c were measured during one clinical review only. Other information obtained was age, sex, body mass index, waist circumference, blood pressure, urine albumin–creatinine ratio, duration since diagnosis and medication.ResultsOne hundred and one patients with DM (type 1 DM = 23, type 2 DM = 78) were included. Spearman's rank correlation coefficient revealed a significant correlation between RBG and HbA1c among the patients with type 2 DM (r = 0.73, P < 0.001) but not patients with type 1 DM (r = 0.17, P = 0.44). Furthermore, in a multivariate linear regression model (R2 = 0.71) RBG (per mmol/l increment) (B = 0.28, 95% CI:0.24–0.32, P < 0.001) was significantly associated with HbA1c among the patients with type 2 DM. Based on ROC analysis (AUC = 0.80, SE = 0.05), RBG ≤7.5 mmol/l was determined as the optimal cut-off value for good glycaemic control (HbA1c <7.0% [53 mmol/mol]) among patients with type 2 DM (sensitivity = 76.7%; specificity = 70.8%; positive predictive value = 62.2%; negative predictive value = 82.9%).Conclusions
Random blood glucose could possibly be used to assess glycaemic control among patients with type 2 DM in rural settings of sub-Saharan Africa.
No preview · Article · Oct 2014 · Tropical Medicine & International Health
[Show abstract][Hide abstract] ABSTRACT: To investigate whether there is an association between diameter of bacille Calmette-Guérin (BCG) scars and effect of purified protein derivative (PPD) reaction and to determine whether vitamin A (VA) combined vitamin D (VD) supplementation influences the immune response to BCG revaccinated in Chinese infants.
A cross-section and 3-month community-randomised trial was conducted. A total of 5 629 infants at 3, 6 and 12 months of age in Junan County of China were examined for BCG scar formation. Then, 597 revaccinated infants were randomly assigned to supplementation (n=307) and control (n=290) groups. The supplementation group were daily assigned to 1 500 IU VA and 500 IU VD for 3 months. Then all infants were subjected to skin test with PPD.
The diameter of BCG scars was positively correlated with diameter of skin indurations of PPD (r=0.17, P<0.05) in the 5 629 infants. The rate of positive response to PPD was higher in the supplementation group than in the control group (96.1% versus 89.7%, P<0.05, prevalence ratio 1.07, 95% CI 1.02-1.12). The prevalence ratio of PPD response for the supplementation group compared with that for the control group was 1.07 (95% CI 1.01-1.13) for the males and 1.08 (95% CI 1.00-1.17) for the females. For the supplementation group, the males got larger tuberculin induration than the females [(0.73±0.21) cm versus (0.67±0.20) cm, P<0.05) after intervention.
The diameter of BCG scars was effectively correlated with PPD response, which indicates BCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention. VA combined VD supplementation may play an immuno-regulatory role in BCG revaccination. This may contribute to the prevention of childhood tuberculosis.
Preview · Article · Feb 2014 · Asian Pacific Journal of Tropical Medicine
[Show abstract][Hide abstract] ABSTRACT: Gestational diabetes mellitus (GDM) - a transitory form of diabetes first recognised during pregnancy complicates between < 1% and 28% of all pregnancies. GDM has important short and long-term health consequences for both the mother and her offspring. To prevent adverse pregnancy outcomes and to prevent or delay, future onset of type 2 diabetes in mother and offspring, timely detection, optimum treatment, and preventive postpartum care and follow-up is necessary. However the area remains grossly under prioritised.
To investigate determinants and barriers to GDM care from initial screening and diagnosis, to prenatal treatment and postpartum follow-up, a PubMed database search to identify quantitative and qualitative studies on the subject was done in September 2012. Fifty-eight relevant studies were reviewed.
Adherence to prevailing GDM screening guidelines and compliance to screening tests seems sub-optimal at best and arbitrary at worst, with no clear or consistent correlation to health provider, health system or client characteristics. Studies indicate that most women express commitment and motivation for behaviour change to protect the health of their unborn baby, but compliance to recommended treatment and advice is fraught with challenges, and precious little is known about health system or societal factors that hinder compliance and what can be done to improve it. A number of barriers related to health care provider/system and client characteristics have been identified by qualitative studies. Immediately following a GDM pregnancy many women, when properly informed desire and intend to maintain healthy lifestyles to prevent future diabetes, but find the effort challenging. Adherence to recommended postpartum screening and continued lifestyle modifications seems even lower. Here too, health care provider, health system and client related determinants and barriers were identified. Studies reveal that sense of self-efficacy and social support are key determinants.
The paper identifies and discusses determinants and barriers for GDM care, fully recognising that these are highly dependent on the context.
Full-text · Article · Jan 2014 · BMC Pregnancy and Childbirth
[Show abstract][Hide abstract] ABSTRACT: A study of health facility (HF) data on women receiving sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) was carried out at antenatal care (ANC) clinics in Mkuranga and Mufindi districts.
A review of health management information system (HMIS) registers, interviews with health-care workers (HWs) and district and national level malaria control program managers corroborated by inter-temporal assessment through observations at HF levels. Statistical data were analyzed in Excel and interpreted in triangulation with qualitative data from interviews and observations.
Data indicated that IPTp doses administered to women were inadequate and partly inconsistent. HMIS registers lacked space for IPT records, forcing HWs to manipulate their record-keeping. The proportion/number of IPTp recipients in related to the supply of SP for free delivery, to women's attendance behaviours, showed showed variation by quarter and year of reporting.
It is impossible to achieve rational health service planning when the HMIS is weak. Whilst it is acknowledged that the HMIS is already overloaded, concerted measures are urgently needed to accommodate data on new interventions and other vertical programs if malaria programs are to achieve their goals.
Full-text · Article · Jan 2014 · Reproductive Health
[Show abstract][Hide abstract] ABSTRACT: Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs).
Sixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining HMM and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs.
The interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients' transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level.
Combining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.
[Show abstract][Hide abstract] ABSTRACT: Plasmodium vivax malaria was common in Greece until the 1950s with epidemics involving thousands of cases every year. Greece was declared free of malaria by the World Health Organization in 1974. From 1974 to 2010, an average of 39 cases per year were reported, which were mainly imported. However, in 2009 and 2010 six and one autochthonous cases were reported culminating with a total of 40 autochthonous cases reported in 2011, of which 34 originated from a single region: Laconia of Southern Peloponnese. In this study the genotypic complexity of the P. vivax infections from the outbreak in Greece during 2011 is described, to elucidate the possible origin and spread of the disease.
Three polymorphic markers of P. vivax were used; Pvmsp-3alpha and the microsatellites m1501 and m3502 on P. vivax isolates sampled from individuals diagnosed in Greece. Thirty-nine isolates were available for this study (20 autochthonous and 19 imported), mostly from Evrotas municipality in Laconia region, in southern Greece, (n = 29), with the remaining representing sporadic cases originating from other areas of Greece.
Genotyping the Evrotas samples revealed seven different haplotypes where the majority of the P. vivax infections expressed two particular Pvmsp-3alpha-m1501-m3502 haplotypes, A10-128-151 (n = 14) and A10-121-142 (n = 7). These haplotypes appeared throughout the period in autochthonous and imported cases, indicating continuous transmission. In contrast, the P. vivax autochthonous cases from other parts of Greece were largely comprised of unique haplotypes, indicating limited transmission in these other areas.
The results indicate that several P. vivax strains were imported into various areas of Greece in 2011, thereby increasing the risk of re-introduction of malaria. In the region of Evrotas ongoing transmission occurred exemplifying that further control measures are urgently needed in this region of southern Europe. In circumstances where medical or travel history is scarce, methods of molecular epidemiology may prove highly useful for the correct classification of the cases.