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ABSTRACT: A few studies have suggested that thymus atrophy is associated with severe malnutrition and increased morbidity; however, no study of thymus size has been undertaken in countries with high mortality. This study examined the relation between thymus size at birth and subsequent mortality in an urban West African community. The size of the thymus was assessed by sonography as a volume estimate, the thymus index. A total of 278 children born at the local health centre in Bandim in Bissau, Guinea-Bissau, was enrolled in the study. Children were followed to the age of 2 y. Thymus size at birth was associated with most strongly weight, as well as with length and arm circumference. Controlling for weight and other risk factors, boys had larger thymus indices than girls [means ratio (MR) = 1.07, 95% confidence interval (95% CI) 1.01-1.14)]. Thymus size was also associated with prematurity, ethnic group, season and investigator, but not with birth order, mother's age, socioeconomic factors or the use of health services. Infant mortality was 117/1000. In a multivariate analysis, excluding premature infants and adjusting for age, gender, ethnic group, season of birth and investigator, higher birthweight (MR = 0.35, 95% CI 0.16-0.74) and larger thymus size (MR = 0.17, 95% CI 0.06-0.48) were independently associated with lower infant mortality. When both indices were estimated in the same model, the thymus index was associated with infant mortality (MR = 0.27, 95% CI 0.07-1.00), whereas birthweight had a non-significant effect (MR = 0.59, 95% CI 0.24-1.47). After 1 y of age neither birthweight nor thymus size at birth was associated with mortality. CONCLUSION: As all deaths were due to infectious diseases, thymus size at birth may be an important predictor of immune competence. Future studies should examine the determinants of thymus growth.
Acta Paediatrica 02/2002; 91(6):698-703. · 2.07 Impact Factor
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Allergy 09/2001; 56(8):800-1. · 6.27 Impact Factor
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ABSTRACT: Tuberculosis (TB) is an increasing global problem, despite effective drug therapies. Access to TB therapy during conflict situations has not been studied.
To determine the effect of irregular TB treatment due to an armed conflict in Guinea-Bissau, West Africa.
Ongoing retrospective cohort study conducted in the capital city of Bissau among 101 patients with TB who received irregular or no treatment during the civil war (war cohort; June 7-December 6, 1998) and 108 patients with TB who received treatment 12 months earlier (peace cohort; June 7-December 6, 1997) and comparison of an additional 42 patients who had completed treatment before June 6, 1998, and 69 patients who had completed treatment before June 6, 1997.
Mortality rates, compared by irregular (war cohort) vs regular (peace cohort) access to treatment, by intensive vs continuation phase of treatment, and by those who had previously completed treatment for TB.
Irregular treatment was associated with an increased mortality rate among patients with TB. The mortality rate ratio (MR) was 3.12 (95% confidence interval [CI], 1.20-8.12) in the war cohort, adjusting for age, sex, human immunodeficiency virus (HIV) infection, residence, and length of treatment. Each additional week of treatment before the war started increased probability of survival by 5% (95% CI, 0%-10%). In the intensive phase of treatment, the adjusted MR was 3.30 (95% CI, 1.04-10.50) and in the continuation phase it was 2.26 (95% CI, 0.33-15.34). Increased mortality among the war cohort was most marked in HIV-positive patients, who had an adjusted MR of 8.19 (95% CI, 1.62-41.25). Mortality was not increased in HIV-positive or HIV-negative patients who had completed TB treatment when the war started.
Interruption of treatment had a profound impact on mortality among patients with TB during the war in Guinea-Bissau. Regular treatment for TB was associated with significantly improved survival for HIV-infected individuals. In emergencies, it is crucial to ensure availability of TB drugs.
JAMA The Journal of the American Medical Association 09/2001; 286(5):599-603. · 30.03 Impact Factor
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ABSTRACT: Raoul Follereau Hospital, Bissau, Guinea-Bissau.
To study the long-term outcome of patients with bacteriologically verified tuberculosis (TB), with or without human immunodeficiency virus (HIV) co-infection.
Sputum samples were collected from all patients referred to the hospital with clinical symptoms of pulmonary tuberculosis. Direct microscopy and culture was performed at the Health Laboratory. Patients with a culture positive for Mycobacterium tuberculosis were followed for 3 years, and underlying factors were analysed regarding the outcome of treatment. A group of sex and age-matched HIV-negative individuals was used as controls.
Of 206 bacteriologically verified pulmonary TB patients, 168 were followed up. Antibodies to HIV-2 were found in 33 patients (19.6%); eight patients (4.8%) had antibodies to HIV-1 or showed dual reactivity. Of 149 patients discharged to follow ambulatory treatment, the survival rate of HIV-2-positive patients was 42.3% (11/26) and for HIV-negative patients it was 81.9% (95/116). The difference in survival between HIV-2-positive and HIV-negative patients was highly significant (P < 0.00001). HIV-negative TB patients had a significantly higher mortality than their controls (mortality ratio 3.75, 95% confidence interval 1.58-8.90). Most patients who survived, regardless of HIV status, also became free from symptoms compatible wtih pulmonary TB.
Although the mortality rate among HIV-positive TB patients was very much higher than among HIV-negative patients, there are weighty arguments for active contact tracing and effective treatment of all TB patients.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2000; 4(9):845-52. · 2.73 Impact Factor
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ABSTRACT: Because the seroprevalence of HIV-2 has been shown to be high in older age groups, we conducted a survey of all persons aged 50 years or over in two districts in Bissau, investigating the presence of HIV antibodies and possible risk factors for HIV infection with a particular emphasis on age, the impact of the war of independence (1963-74), traditional marital and extramarital sex patterns, blood contact and contact with monkeys. In 670 participants, the HIV-2 prevalence was 14.3%; 16.1% in women and 12.3% in men. The HIV-1 prevalence was only 0.5% (3/670). The HIV-2 prevalence peaked for men in the 60-69 years age group, and for women in the 50-59 years age group, declining markedly in the following age group for both men and women (OR = 0.09 (0.01-0.51), OR = 0.37 (0.15-0.82), respectively). This pattern could be due to differential mortality for HIV-2 infected individuals or to a cohort effect for a generation who were sexually active at the time of the war of independence in the 1960s and early 1970s in Bissau. Supporting the link with the colonial army, women who had had sex with a white man had a higher seroprevalence (OR = 3.63 (1.12-11.24)). The ethnic group indigenous to Bissau city had a much lower prevalence, but demographic and cultural risk factors such as marital status, religion, education and having lived outside Bissau were not associated with HIV-2. In the multivariate analyses for women, variables related to extramarital sex or prostitution (having sex with a white man, having lived in Senegal, not living with husband, and not marrying first sexual partner) were associated with higher risk. For men, previous spouses who had died or had divorced were associated with higher prevalence. Having married the first sexual partner was protective against HIV-2 infection for both men (OR = 0.29 (0.09-0.76)) and women (OR = 0.19 (0.04-1.00)). Hospitalizations, possibly due to transfusions, tended to be associated with higher risk, but only for women (OR = 1.83 (0.97-3.48)). The focus of the HIV-2 epidemic in Guinea-Bissau is likely to be endogenous, and the war of independence and the colonial army with its associated prostitution may have played an important part in propagating the virus.
Scandinavian Journal of Infectious Diseases 02/2000; 32(2):169-75. · 1.72 Impact Factor
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ABSTRACT: To study the effects on children of humanitarian aid agencies restricting help to refugee families (internally displaced people).
Follow up study of 3 months.
Prabis peninsular outside Bissau, the capital of Guinea-Bissau, which has functioned as a refugee area for internally displaced people in the ongoing war, and the study area of the Bandim health project in Bissau.
422 children aged 9-23 months in 30 clusters. Main outcome measures: Mid-upper arm circumference and survival in relation to residence status.
During the refugee situation all children deteriorated nutritionally, and mortality was high (3.0% in a 6 week period). Rice consumption was higher in families resident in Prabis than in refugees from Bissau but there was no difference in food expenditure. Nutritional status, measured by mid- upper arm circumference, was not associated with rice consumption levels in the family, and the decline in circumference was significantly worse for resident than for refugee children; the mid-upper arm circumference of refugee children increased faster than that of resident children. For resident children, mortality was 4.5 times higher (95% confidence interval 1.1 to 30.0) than for refugee children. Mortality for both resident and refugee children was 7.2 times higher (1.3 to 133.9) during the refugee's stay in Prabis compared with the period after the departure of the refugees.
In a non-camp setting, residents may be more malnourished and have higher mortality than refugees. Major improvements in nutritional status and a reduction in mortality occurred in resident and refugee children as soon as refugees returned home despite the fact that there was no improvement in food availability.
BMJ 11/1999; 319(7214):878-81. · 14.09 Impact Factor
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ABSTRACT: Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children.
Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound.
Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months.
Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.
The Lancet 02/1999; 353(9147):98-102. · 38.28 Impact Factor
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ABSTRACT: To examine whether clinical symptoms, including rash, were more common after measles immunization compared with placebo and to study the association between postvaccination symptoms and later mortality.
Examination of side effects in the 3 weeks after immunization in a trial of high titer and standard titer measles vaccines.
Two hundred twenty-four children randomly selected to be included in the surveillance for diarrhea, fever and rash.
There was no difference in fever and diarrhea between recipients of high titer vaccines and recipients of placebo. However, high titer recipients tended to have more measles-like rashes than placebo recipients [relative risk, 2.12 (range, 0.90 to 5.03)]. Among recipients of high titer vaccines, children who presented a rash had higher mortality in the following 5 to 7 years than those who did not develop rash [mortality rate ratio, 3.85 (range, 1.52 to 9.79)]. High titer recipients without a rash had the same mortality as children in the placebo group who were given standard doses of measles vaccine at 10 months of age [mortality rate, 0.76 (range, 0.35 to 1.62)].
These observations suggest that in this particular study, rash after high titer measles vaccine may identify children who received a particularly high dose of vaccine or children with more severe and persistent postvaccination immunosuppression. Whether high titer vaccine is more likely than standard titer measles vaccine to provoke such reaction is not known, given that we did not compare side effects after different titers of measles vaccine. Future trials of live measles vaccine should monitor the development of rash.
The Pediatric Infectious Disease Journal 02/1999; 18(1):48-52. · 3.58 Impact Factor
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ABSTRACT: Recent studies of HIV-2 have suggested an increased incidence and prevalence among women older than 45 y compared with younger women. We therefore examined whether this phenomenon applied generally to all 3 major retroviruses, HIV-1, HIV-2 and HTLV-I, among women in Africa. We conducted a MedLine search from 1987 to 1997, using the keywords Africa and HIV-1, HIV-2 or HTLV, respectively. Community studies, national surveys and studies on professional cohorts were selected. Age groups > 45/50 y were compared with the age group with the lowest female/male prevalence ratio between 20 and 44 y of age. Thirty-one studies had sufficient data to be included. The female/male odds ratio (OR) for seropositivity was calculated for the old and the young age groups, respectively, providing the ratio of odds ratios: OR (old)/OR (young). Summary ratios for studies of all 3 retroviruses were estimated. In general we found a higher female/male prevalence ratio in the age group over 45/50 y than in the younger age group. For HIV-1 the odds ratio was 1.82 times [95% confidence interval (CI) 1.19-2.79] higher in the old age group than in the young group. For HIV-2 it was 1.97 [95% CI 0.95-4.08], and for HTLV-I it was 2.02 [95% CI 0.99-4.14] times higher. For all 3 viruses combined, the ratio was 1.88 [95% CI 1.36-2.61]. The few incidence studies of HIV-1 and HIV-2 indicated a similar tendency. Since differential mortality is unlikely to explain the pattern, the increase in the HIV-1, HIV-2 and HTLV-I female/male prevalence ratio suggests that older women may have increased exposure or susceptibility to all 3 retrovirus infections.
Scandinavian Journal of Infectious Diseases 01/1999; 31(5):459-66. · 1.72 Impact Factor
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ABSTRACT: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy.
Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test.
Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season.
Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.
The Pediatric Infectious Disease Journal 01/1999; 18(1):53-7. · 3.58 Impact Factor
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ABSTRACT: We present the results of a 6-year study of 131 human immunodeficiency virus (HIV) type 2 (HIV-2)-infected individuals from a rural population in Guinea-Bissau. Proviral DNA sequences 1.3 kb in length were obtained from each individual and, together with clinical data, including proviral load and CD4 and CD8 levels, were used to assess whether viral genotype influences clinical outcome. With a phylogenetic model, a correlation was found between viral genotype and mortality; this correlation was not due to confounding factors, such as age-specific viral strains or cohabitation of patients. The data provide strong evidence for the involvement of viral genetic factors in determining HIV disease progression in vivo. The pattern of association found suggests that virulence factors are multiple and scattered throughout the HIV-2 genome and can be rapidly gained or lost by the virus through a combination of mutation and recombination. These findings may lead to the identification of viral determinants of HIV disease progression.
Journal of Virology 11/1998; 72(10):7895-9. · 5.40 Impact Factor
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ABSTRACT: To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non-seroresponders. These changes were more marked among girls, since they had significantly higher CD4 percentages and CD4/CD8 ratios than boys in the convalescence phase. In conclusion, measles infection is not associated with a long-term suppression of CD4+ or CD8+ T-lymphocytes.
Scandinavian Journal of Infectious Diseases 02/1998; 30(1):17-21. · 1.72 Impact Factor
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ABSTRACT: To determine risk factors for diarrhea, the authors followed an open cohort of 1,314 children from Guinea-Bissau by weekly diarrhea recall interviews between April 1987 and March 1990. Data on feeding practices and measles infection were available for all children and, for 531 children, comprehensive data on explanatory variables were recorded. Of 57 variables, seven were independently associated with an increased incidence of diarrhea. These were a recent (in the past 14 days) diarrheal episode, male sex, being weaned from breast milk, not being looked after by the mother, head of the household being < 30 years old, eating cold leftovers, and drinking water from an unprotected public water supply. In breastfed children, only three variables were associated with diarrhea, including prior diarrhea, male sex, and not being looked after by the mother. Among weaned children, six variables delineated increased rates of diarrhea, including unprotected public water supply, eating of cold leftovers, and lack of maternal education. Major determinants of persistent diarrhea included weaning, lack of maternal education, and having pigs in the home. It is concluded that, in addition to the promotion of breastfeeding, important interventions against diarrhea include improvements in water supply, hygiene, and food handling. However, because of effect modification by breastfeeding, the largest effects of these interventions will probably be among weaned children.
American Journal of Epidemiology 08/1997; 146(3):273-82. · 5.22 Impact Factor
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AIDS 07/1997; 11(7):939-40. · 6.24 Impact Factor
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ABSTRACT: Community studies with 1-3 years of follow-up have reported four to five times higher mortality in HIV-2-infected than in uninfected adults. In a cohort study of HIV-1, an increasing difference in mortality rates of HIV-1-infected and uninfected individuals is expected over time, because of rising mortality with advancing HIV-1 infection. We therefore investigated long-term survival of HIV-2-infected adults.
Adults enrolled in 1987 in a community study of HIV-2 infection in Guinea-Bissau were followed up with serological surveys in 1989 and 1992. Survival was assessed in 1995, 9 years after enrollment.
The annual incidence of HIV-2 was 0.7% for adults and tended to be higher for older individuals than for participants aged 15-44 years (relative risk 3.21 [95% CI 0.91-11.37]). With control for age, HIV-2-infected adults had twice as high mortality as uninfected individuals (mortality ratio 2.32 [1.18-4.57]); the mortality ratio was highest in the first year of the study (4.50 [1.31-15.43]). The difference between infected and uninfected individuals was stronger for adults under 45 years of age (mortality ratio 4.72 [1.86-11.97]) than for older people (1.35 [0.51-3.56]). HIV-2-infected individuals living with an infected spouse had significantly higher mortality than HIV-2-infected individuals living with an uninfected spouse (p = 0.027).
HIV-2-associated mortality is not increasing with length of follow-up. Mortality in HIV-2-infected adults is only twice as high as that in uninfected individuals. In the majority of adults, HIV-2 has no effect on survival.
The Lancet 04/1997; 349(9056):911-4. · 38.28 Impact Factor
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P Aaby,
K Ariyoshi,
M Buckner, H Jensen,
N Berry,
A Wilkins,
D Richard,
O Larsen,
F Dias,
M Melbye,
H Whittle
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ABSTRACT: To examine whether proviral load is important for transmission between spouses, since we have previously found that the proviral load of HIV-2 predicts the severity of infection.
Proviral load was examined in 121 HIV-2-infected adults in a rural area of Guinea-Bissau. For the 68 subjects who had a spouse of known HIV status the risk of the spouse being infected was examined.
Statistical methods for dependent data were used, because several couples were polygamous.
Twenty-seven HIV-2-infected men had 52 current wives of whom 17 (33%) were HIV-2-seropositive. Forty-one HIV-2-infected women had 36 current husbands of known HIV serostatus; nine (25%) were HIV-2-positive. In univariate analyses, concordance of female partners of HIV-2-infected men increased with a previous history of prostitution, age of wife, lack of age difference between the spouses, number of previous husbands, number of wives of the man, and the proviral load. The only significant predictor of concordance in multivariate analyses when wives with a history of prostitution were excluded was an age of 45 years or older [odds ratio (OR), 8.68; 95% confidence interval (CI), 2.34-32.22]. This tendency was not explained by the length of current marriage. Although husbands with a high proviral load were more likely to have concordant spouses than those with a low proviral load (< 20 copies/10(5) CD4 cells), this association was not statistically significant (OR, 2.59; 95% CI, 0.90-7.46). Among spouses of HIV-2-infected women, none of the examined factors, including previous prostitution or proviral load in the woman, predicted whether the husband was HIV-2-infected.
Women appear to be more susceptible to HIV-2 infection after 40-45 years of age. The apparent change in susceptibility may be a major reason for the distinctive age pattern of HIV-2 infection observed in West Africa.
AIDS 11/1996; 10(13):1585-90. · 6.24 Impact Factor
