Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study.

BACKGROUND: Microscopic colitis, comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhoea. The long-term prognosis is not well described. AIM: To study outcome of symptoms and health-related quality of life (HRQoL). METHODS: A case-control study using a postal questionnaire with three population-based controls per patient matched for age, sex and municipality. HRQoL was assessed by the Short Health Scale (SHS). Patients in clinical remission, defined as a mean of <3 stools/day, were evaluated separately (CC; n = 72, LC; n = 60). RESULTS: The study included 212 patients and 627 matched controls. Median disease duration was 5.9 (range 0.5-27) years and 6.4 (0.3-14.8) years for CC and LC respectively. Abdominal pain, fatigue, arthralgia, myalgia, faecal incontinence and nocturnal defecation were significantly more prevalent in CC patients compared with controls. These differences persisted in CC patients in clinical remission with respect to abdominal pain (36% vs. 21%), fatigue (54% vs. 34%), arthralgia (61% vs. 41%) and myalgia (53% vs. 37%). In LC patients, abdominal pain, fatigue, faecal incontinence and nocturnal defecation were more prevalent compared with controls. In LC patients in clinical remission, fatigue was more prevalent compared with controls (54% vs. 37%). These differences were statistically significant (P < 0.05). All four HRQoL dimensions (symptom burden, social function, disease-related worry, general well-being) were impaired in patients with active CC and LC. CONCLUSIONS: Although considered to be in clinical remission, patients with microscopic colitis suffer from persisting symptoms such as abdominal pain, fatigue, arthralgia or myalgia several years after diagnosis.

Mucosal healing and mortality in coeliac disease.

BACKGROUND: Coeliac disease (CD), characterised by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery. AIMS: To determine whether persistent VA is associated with mortality in CD. METHODS: Through biopsy reports from all pathology departments (n = 28) in Sweden, we identified 7648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We used Cox regression to examine mortality according to follow-up biopsy. RESULTS: The mean age of CD diagnosis was 28.4; 63% were female; and the median follow-up after diagnosis was 11.5 years. The overall mortality rate of patients who underwent follow-up biopsy was lower than that of those who did not undergo follow-up biopsy (Hazard Ratio 0.88, 95% CI: 0.80-0.96). Of the 7648 patients who underwent follow-up biopsy, persistent VA was present in 3317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared with those with mucosal healing (HR: 1.01; 95% CI: 0.86-1.19). Mortality was not increased in children with persistent VA (HR: 1.09 95% CI: 0.37-3.16) or adults (HR 1.00 95% CI: 0.85-1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80-1.14). CONCLUSIONS: Persistent villous atrophy is not associated with increased mortality in coeliac disease. While a follow-up biopsy will allow detection of refractory disease in symptomatic patients, in the select population of patients who undergo repeat biopsy, persistent villous atrophy is not useful in predicting future mortality.

Appendicectomy and multiple sclerosis risk.

BACKGROUND: Appendicectomy for acute appendicitis, but not for other causes, is inversely associated with immune-mediated diseases such as ulcerative colitis, suggesting appendicitis is a marker of immune characteristics influencing immune-mediated disease risk. This study investigated the association of appendectomy and its underlying diagnosis with multiple sclerosis (MS). METHODS: Swedish general population registers and the Swedish MS register provided information on 20,542 cases with MS diagnosed between 1964-2006 and 204,157 controls matched for age, sex, period and region. Appendicectomy prior to MS diagnosis was identified in 673 cases and 6518 controls. Conditional logistic regression, with adjustment for socio-economic index, assessed the association of diagnosis underlying appendicitis with MS risk. RESULTS: A perforated appendix, the best indicator of acute appendicitis in this material, was inversely associated with MS, although not statistically significantly, with an odds ratio (and 95% confidence interval of 0.86 (0.70-1.04). The odds ratios are 1.04 (0.94-1.16) for appendicitis without perforation and 1.14 (0.98-1.33) for appendectomy without appendicitis. CONCLUSION: Although inconclusive in terms of assessing the hypothesis, these results may help to explain why earlier studies of appendicitis and MS risk have been inconsistent, as there may be variation in association by diagnosis underlying appendicectomy.

The burden of hepatitis C in Sweden: a national study of inpatient care.

The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43,000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215,000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.

Anger, depression and anxiety associated with endothelial function in childhood and adolescence.

OBJECTIVE: Psychosocial adversity is a risk factor for cardiovascular disease (CVD) in adults. The authors assessed associations of reactive hyperaemia peripheral arterial tonometry (RH-PAT), a measure of endothelial function predictive of CVD, with self-assessed psychological health among school children. METHODS: A total of 248 healthy school children (mean (SD) age 14.0 (1.0); 136 girls and 112 boys) underwent RH-PAT testing. They completed the Beck Youth Inventories (BYI) of emotional and social impairment scales, which is used to screen for depression, anxiety, anger and disruptive behaviour. RESULTS: No sex differences were observed for the RH-PAT score. Statistically significant differences were observed for the BYI scores; girls had higher scores for depression, anger and anxiety. Among the girls, there were statistically significant associations between lower RH-PAT scores and higher scores for anger (B coefficient=-0.100, p=0.040), depression (-0.108, p=0.009) and anxiety (-0.138, p=0.039) after adjustment for age. Among the boys, disruptive behaviour was associated with higher RH-PAT scores (0.09, p=0.006). CONCLUSIONS: The girls have higher levels of self-assessed anger; depression and anxiety compared with the boys, and these characteristics are associated with lower RH-PAT scores, indicating attenuated endothelial function. Among the boys, disruptive behaviour was associated with better endothelial function. Although psychological ill-health is associated with impaired endothelial function and CVD among adults, such processes may also be relevant to children. Psychosocial adversity in childhood might be a risk factor for subsequent CVD.

Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring.

Breast milk contains pro- and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (CBMCs) and intestinal epithelial cells (IECs, cell line HT-29) to microbial challenge. Ninety-five women were included: 30 from Mali in West Africa, 32 Swedish immigrants and 33 native Swedish women. CBMCs or IECs were stimulated in vitro with breast milk, alone or in combination with lipopolysaccharide (LPS) or peptidoglycan (PGN). Breast milk in general abrogated the LPS-induced down-regulation of surface CD14 and Toll-like receptor (TLR)-4 expression on CB monocytes, while inhibiting the PGN-induced TLR-2 up-regulation. However, breast milk from immigrant women together with LPS induced a lower CBMC release of interleukin (IL)-6 (P = 0·034) and CXCL-8/IL-8 (P = 0·037) compared with breast milk from Swedish women, while breast milk from Swedish women and Mali women tended to increase the response. The same pattern of CXCL-8/IL-8 release could be seen after stimulation of IECs (HT-29). The lower CBMC and IEC (HT-29) responses to microbial compounds by breast milk from immigrant women could be explained by the fact that breast milk from the immigrant group showed a divergent pro- and anti-inflammatory content for CXCL-8/IL-8, transforming growth factor-ß1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses.

Cancer risk among patients with multiple sclerosis and their parents.

BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

Breast-feeding and a subsequent diagnosis of measles.

BACKGROUND: Breast-feeding protects against many infectious diseases and may also influence immunization outcomes. AIM: This study investigated if breast-feeding protects against clinical measles and if it modified the effect of immunization. METHODS: We used logistic regression with data for 10 207 individuals from the 1970 British Cohort study (BCS70). Breast-feeding data were collected at five years of age, and information on clinical measles infection, as well as socio-economic measures was collected at the age of ten years. Breast feeding was categorized as: breast-fed <1 month (n = 1611), breast-fed for 1-3 months (n = 1016), breast-fed for more than three months (n = 1108), breast-feeding of uncertain duration (n = 21) and never breast-fed (n = 6451). RESULTS: Breast-feeding for more than three months was negatively associated with a diagnosis of clinical measles infection after adjustment for crowding, social class, measles vaccination, parity and sex with an odds ratio (95% confidence interval) of 0.69 (0.60-0.81) compared with those who never breast-fed. Measles vaccination was highly associated with low risk for measles with: 0.14 (0.13-0.16). Age at acute measles infection was not associated with breastfeeding. Breast-feeding did not notably alter measles immunization efficacy. CONCLUSION: Immunization against measles provides effective protection against the disease. A more modest reduction in the risk of a measles diagnosis is associated with breast-feeding. The associations with a diagnosis of measles for breast-feeding and measles immunization are independent of each other.

Epstein-Barr virus and cytomegalovirus are differentially associated with numbers of cytokine-producing cells and early atopy.

BACKGROUND: We have previously shown that Epstein-Barr virus (EBV) seropositivity, at 2 years of age, was inversely related to IgE-sensitization and that this effect was enhanced when EBV is combined with cytomegalovirus (CMV) seropositivity. We hypothesize that early exposure to EBV or CMV will affect the cytokine balance in the individual. OBJECTIVE: The aim of this study was to relate the cytokine profile in peripheral blood mononuclear cells (PBMC) to the EBV and CMV serostatus and IgE-sensitization in children at 2 years of age. METHODS: Seventy-five children were followed prospectively from birth until 2 years of age. Their EBV and CMV serostatus was correlated to the numbers of IFN-gamma, IL-4, IL-10 and IL-12-producing PBMC following PHA stimulation in vitro. Skin prick tests and allergen-specific IgE antibodies were used to assess IgE-sensitization. RESULTS: In the study cohort, there was an inverse association between EBV seropositivity and IgE-sensitization but not with CMV seropositivity. Following linear regression analysis, we did not detect any statistically significant associations between children with IgG antibodies against EBV at 2 years of age and the investigated cytokines. However, there was a non-significant tendency to a positive association between high numbers of all individual cytokine-producing cells and EBV seropositivity. Children who were CMV seropositive had significantly higher numbers of IFN-gamma and lower numbers of IL-4-producing cells compared with CMV negative children. There was a significant, positive association between the number of IL-4-producing cells and IgE-sensitization. CONCLUSION: Taken together our results indicate that infections with EBV and CMV in different ways will interact with the immune system and may protect children from developing early atopy.

Maternal smoking during pregnancy and multiple sclerosis amongst offspring.

INTRODUCTION: An association between parental smoking and multiple sclerosis (MS) in offspring has been reported. This study examined whether maternal smoking during pregnancy is associated with MS in offspring. METHODS: Swedish general population registers provided prospectively recorded information on maternal smoking during pregnancy. The study identified 143 cases with MS diagnosed by 2006 and 1730 matched controls. Subjects were born since 1982 and individually matched by year of birth, age, sex and region of residence. Conditional logistic regression assessed the association of maternal smoking with MS in offspring with adjustment for socioeconomic index. RESULTS: Maternal smoking during pregnancy was not associated with MS in offspring, with an odds ratio (and 95% confidence interval) of 0.96 (0.65-1.44). When stratified by paediatric or later MS onset there was no association with maternal smoking in either stratum. CONCLUSION: It is unlikely that smoking during pregnancy represents a risk for early-onset MS amongst offspring.

Mental health and resilience at older ages: bouncing back after adversity in the British Household Panel Survey.

BACKGROUND: Resilience is having good outcomes despite adversity and risk and could be described in terms of preserving the same level of the outcome or rebounding back to that level after an initial set back. Using the latter definition, resilience as "bouncing back", this paper aims (1) to identify those members of a panel survey who demonstrated resilience, and (2) to identify the characteristics of the resilient individuals and the predictors of their resilience. METHODS: The study subjects were the 3581 participants in the British Household Panel Survey, selected from waves 1-14, who satisfied three requirements: exposure to an adversity; availability of consecutive General Health Questionnaire (GHQ)-12 scores; aged 50 or more years. The primary outcome variable was resilience, operationalised as a GHQ-12 score that increased after exposure to adversity and returned to its pre-exposure level in the next (after 1 year) wave of the survey. The adversities were: functional limitation; bereavement or marital separation; poverty. RESULTS: The prevalence of resilience, as defined, was 14.5%. After adjusting for regression to the mean, the GHQ-12 score of the resilient dropped by a mean of 3.6 points in the post-adversity period. Women predominated among the resilient, with this gender difference stronger among older women than younger women. The resilient were more likely to have high social support than the non-resilient, but otherwise were not different socioeconomically. High social support pre-adversity and during adversity increased the likelihood of resilience by 40-60% compared with those with low social support. CONCLUSIONS: Resilience is relatively rare and favours older women. It is fostered by high levels of social support existing before exposure to adversity.

Coeliac disease and risk of sepsis.

OBJECTIVE: To examine the risk of subsequent sepsis in individuals with coeliac disease. DESIGN: We used Swedish national health registers to identify 15 325 individuals with a diagnosis of coeliac disease (1964-2003) and 14 494 inpatient reference individuals. Cox regression estimated the hazard ratios (HRs) for subsequent sepsis. RESULTS: Compared with inpatient reference individuals, individuals with coeliac disease were at increased risk of sepsis (HR = 1.6, 95% confidence interval (95% CI) = 1.2 to 1.9, p<0.001). The highest risk estimates were seen for pneumococcal sepsis (HR = 2.5, 95% CI = 1.2 to 5.1, p = 0.014). Individuals with coeliac disease diagnosed in childhood were not at increased risk of subsequent sepsis (HR = 1.0, 95% CI = 0.6 to 1.9, p = 0.908). When individuals with coeliac disease were compared with reference individuals from the general population, coeliac disease was associated with an increased risk of sepsis (HR = 2.6, 95% CI = 2.1 to 3.0, p<0.001). The HR for pneumococcal sepsis was 3.9 (95% CI = 2.2 to 7.0, p<0.001). In this comparison, children with coeliac disease were also at an increased risk of sepsis (HR = 1.8, 95% CI = 1.2 to 2.7, p = 0.003). CONCLUSION: This study showed a modestly increased risk of sepsis in patients with coeliac disease with the highest risk for pneumococcal sepsis. This risk increase was limited to those with coeliac disease diagnosed in adulthood. Potential explanations include hyposplenism, increased mucosal permeability and an altered composition of the intestinal glycocalyx in individuals with coeliac disease.

Decrease of RA-related orthopaedic surgery of the upper limbs between 1998 and 2004: data from 54,579 Swedish RA inpatients.

OBJECTIVES: To describe the overall use and temporal trends in orthopaedic upper limb surgery associated with RA on a nation wide basis in Sweden between 1998 and 2004. METHODS: Data for all inpatient visits during 1998-2004 for patients older than 18 yrs with RA-related diagnoses were extracted from the Swedish National Hospital Discharge Registry (SNHDR). The SNHDR prospectively collects data on all hospital admissions in Sweden according to the International Classification of Diseases (ICD). Data were analysed with respect to orthopaedic surgery of the hand, elbow and shoulder. RESULTS: During the study period, 54,579 individual RA patients were admitted to a Swedish hospital and 9% of these underwent RA-related surgery of the upper limbs. The RA patient cohort underwent a total of 8251 RA-related upper limb surgical procedures. The hand (77%) was most frequently operated on, followed by the shoulder (13%) and the elbow (10%). There was a statistically significant decrease of 31% for all admissions associated with RA-related upper limb surgery during 1998-2004 (P = 0.001). Some 10% of all RA-related upper limb surgery was due to total joint arthroplasties (TJAs), mostly for the elbow (59%). During 1998-2004, all TJAs, elbow-TJAs and shoulder-TJAs had a stable occurrence. In contrast, the overall numbers of hand-TJAs significantly increased (P = 0.009). CONCLUSIONS: Rates of RA-related upper limb surgery decreased and TJAs had a stable occurrence in Sweden during 1998-2004. The findings of this study may reflect trends in disease management and health outcomes of RA patients in Sweden.

Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease.

OBJECTIVES: We investigated the risk of myocarditis, cardiomyopathy, and pericarditis in patients with celiac disease (CD) from a general population cohort. SUBJECTS AND METHODS: Through the Swedish national registers we identified 9363 children and 4969 adults with a diagnosis of CD (1964-2003). These individuals were matched with upto five reference individuals for age, sex, calendar year and county (n = 69 851). Cox regression estimated hazard ratios (HRs) for later heart disease. MAIN OUTCOME MEASURES: Myocarditis, cardiomyopathy (any or dilated), and pericarditis defined according to relevant international classification of disease codes in the Swedish national inpatient register. RESULTS: Celiac disease diagnosed in childhood was not associated with later myocarditis (HR = 0.2; 95% CI = 0.0-1.5), cardiomyopathy of any type (HR = 0.8; 95% CI = 0.2-3.7), or pericarditis (HR = 0.4; 95% CI = 0.1-1.9). Restricting our analyses to adulthood CD and heart disease diagnosed from 1987 and onwards in departments of cardiology/internal medicine, we found no association between CD and later myocarditis (HR = 2.1; 95% CI = 0.4-11.7), dilated cardiomyopathy (HR = 1.7; 95% CI = 0.4-6.5) or pericarditis (HR = 1.5; 95% CI = 0.5-4.0). CONCLUSION: This study found no association between CD, later myocarditis, cardiomyopathy or pericarditis.

Protection against clinical pertussis induced by whole-cell pertussis vaccination is related to primo-immunisation intervals.

AIMS: Information on subjects who had at least three immunisations against pertussis was provided by longitudinal data from the 1970 British Cohort Study (BCS70) and used to assess whether three whole-cell pertussis (wP) immunisations given within less than 5 months confer less effective protection in childhood compared with a schedule with a longer interval. METHODS: Age at pertussis infection was the dependent variable in a Cox regression analysis, to investigate associations with duration between first and third pertussis immunisation; with third immunisation modelled as a time-dependent covariate. Adjustment was for number of pertussis immunisations (three or four), sex, social class and other potential confounding factors. RESULTS: A total of 8545 children were included in the analysis and 556 had a history of whooping cough. A duration of over 4 months between first and third pertussis immunisations is statistically significantly associated with a reduced risk of pertussis infection by age 10 years, compared with three immunisations given over a shorter period, producing a statistically significant adjusted hazard ratio of 0.74 (0.62-0.92). A fourth immunisation against pertussis further enhanced the protective effect with a hazard ratio of 0.59 (0.44-0.82). CONCLUSION: These results were based on a historical UK cohort using wP vaccine, and indicate that a vaccination schedule with an interval between the immunisations greater than 4 months, and also including a fourth immunisation, would be more effective in this population than a three dose schedule within a shorter interval without booster.

Differential regulation of IgG subclasses and IgE antimalarial antibody responses in complicated and uncomplicated Plasmodium falciparum malaria.

The aim of this study was to assess the immunoglobulin (Ig)-subclass distribution of antimalarial antibody responses in 110 and 169 Thai patients with complicated and uncomplicated Plasmodium falciparum malaria, respectively. Antimalarial plasma IgG subclasses and IgE antibody levels against a crude malaria blood stages, and antigen preparation were determined using enzyme-linked immunosorbent assay (ELISA). On admission, the levels of anti-P. falciparum IgG1, IgG2 and IgG3 were significantly lower in patients with complicated malaria than uncomplicated malaria (IgG1, P < 0.0001; IgG2, P < 0.0001; IgG3, P < 0.0001). The levels of antimalarial IgE were slightly lower, but not statistically significant (P = 0.389) in the complicated malaria. After adjusting all antibody levels and age, anti-P. falciparum IgG3 levels remained significantly associated with complicated malaria. None of the other antibody concentrations showed statistically significant associations with complicated malaria. The anti-P. falciparum IgG3 levels were related to the IgG1 as well as IgG2 levels. A correlation between anti-P. falciparum IgG2 and IgE was observed in the complicated malaria group, and this may indicate their roles in the severity of disease. Our data suggest that anti-P. falciparum IgG3 is associated with a reduced risk of complicated malaria and that antimalarial Ig-subclasses are differently regulated in patients with complicated and uncomplicated malaria.

Fc gamma receptor IIa (CD32) polymorphism and antibody responses to asexual blood-stage antigens of Plasmodium falciparum malaria in Sudanese patients.

In a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcgammaRIIa-R/H131 polymorphism and anti-malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria-free controls. Genotyping of FcgammaRIIa-R/H131 dimorphism was performed using gene-specific polymerase chain reaction (PCR) amplification with allele-specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood-stage antigens were assessed by an enzyme-linked immunosorbent assay. The frequency of the FcgammaRIIa-R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcgammaRIIa-H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332-C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcgammaRIIa-R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite-neutralizing immune mechanisms.