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ABSTRACT: The rise in tuberculosis (TB) incidence following generalized HIV epidemics can overwhelm TB control programmes in resource-limited settings, sometimes accompanied by rising rates of drug resistance. This has led to claims that DOTS-based TB control has failed in such settings. However, few studies have described the effect of a sustained and well-supported DOTS programme on TB incidence and drug resistance over a long period. We present long-term trends in incidence and drug resistance in rural Malawi.
Karonga District in northern Malawi has an adult HIV prevalence of ∼10%. A research group, the Karonga Prevention Study, collaborates with the National Tuberculosis Programme to support core TB control activities. Bacteriological, demographic and clinical (including HIV status) information from all patients starting TB treatment in the District have been recorded since 1988. During that period isolates from each culture-positive TB patient were exported for drug sensitivity testing. Antiretroviral therapy (ART) has been widely available since 2005.
Incidence of new smear-positive adult TB peaked at 124/100,000/year in the mid-90s, but has since fallen to 87/100,000/year. Drug sensitivity information was available for 95% (3132/3307) of all culture-positive cases. Initial resistance to isoniazid was around 6% with no evidence of an increase. Fewer than 1% of episodes involved a multi-drug resistant strain.
In this setting with a generalised HIV epidemic and medium TB burden, a well-supported DOTS programme enhanced by routine culture and drug sensitivity testing may well have reduced TB incidence and maintained drug resistance at low levels.
PLoS ONE 01/2013; 8(3):e58192. · 4.09 Impact Factor
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Amelia C Crampin,
Albert Dube,
Sebastian Mboma,
Alison Price,
Menard Chihana,
Andreas Jahn,
Angela Baschieri,
Anna Molesworth,
Elnaeus Mwaiyeghele,
Keith Branson,
Sian Floyd,
Nuala McGrath, Paul E M Fine,
Neil French,
Judith R Glynn,
Basia Zaba
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ABSTRACT: The Karonga Health and Demographic Surveillance System (Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002-2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behaviour, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades.
International Journal of Epidemiology 06/2012; 41(3):676-85. · 6.41 Impact Factor
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The Journal of Infectious Diseases 12/2011; 205(3):515; author reply 517-8. · 6.41 Impact Factor
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Chiea C Khor,
Fredrik O Vannberg,
Stephen J Chapman,
Haiyan Guo,
Sunny H Wong,
Andrew J Walley,
Damjan Vukcevic,
Anna Rautanen,
Tara C Mills,
Kwok-Chiu Chang, [......],
Kevin Marsh,
Kathryn Maitland,
J Anthony Scott,
Thomas N Williams,
James A Berkley,
Sian Floyd,
Nelson L S Tang, Paul E M Fine,
Denise L M Goh,
Adrian V S Hill
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ABSTRACT: The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling.
Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections.
We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P=3.8x10(-11) for all comparisons), with -292 accounting for most of the association signal (P=4.58x10(-7)). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production--that is, 25 to 40% less CISH expression.
Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles.
New England Journal of Medicine 06/2010; 362(22):2092-101. · 53.30 Impact Factor
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ABSTRACT: As HIV-related deaths increase in a population the usual association between low socioeconomic status and child mortality may change, particularly as death rates from other causes decline.
As part of a demographic surveillance system in northern Malawi in 2002-6, covering a population of 32,000, information was collected on socio-economic status of the households. Deaths were classified as HIV/AIDS-related or not by verbal autopsy. Poisson regression models were used to assess the association of socio-economic indicators with all-cause mortality, AIDS-mortality and non-AIDS mortality among children. There were 195 deaths in infants, 109 in children aged 1-4 years, and 38 in children aged 5-15. All-cause child mortality in infants and 1-4 year olds was similar in households with higher and lower socio-economic status. In infants 13% of deaths were attributed to AIDS, and there were no clear trends with socio-economic status for AIDS or non-AIDS causes. For 1-4 year olds 27% of deaths were attributed to AIDS. AIDS mortality was higher among those with better built houses, and lowest in those with income from farming and fishing, whereas non-AIDS mortality was higher in those with worse built houses, lowest in those with income from employment, and decreased with increasing household assets.
In this population, since HIV infection among adults was initially more common among the less poor, childhood mortality patterns have changed. The usual gap in survival between the poor and the less poor has been lost, but because the less poor have been disproportionately affected by HIV, rather than because of relative improvement in the survival of the poorest.
PLoS ONE 01/2010; 5(6):e11320. · 4.09 Impact Factor
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Sunny H Wong,
Sailesh Gochhait,
Dheeraj Malhotra,
Fredrik H Pettersson,
Yik Y Teo,
Chiea C Khor,
Anna Rautanen,
Stephen J Chapman,
Tara C Mills,
Amit Srivastava, [......],
Benjamin P Fairfax,
Julian C Knight,
Philip C Hill,
Richard A Adegbola,
Hakon Hakonarson, Paul E M Fine,
Ramasamy M Pitchappan,
Rameshwar N K Bamezai,
Adrian V S Hill,
Fredrik O Vannberg
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ABSTRACT: Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.
PLoS Pathogens 01/2010; 6:e1000979. · 9.13 Impact Factor
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ABSTRACT: Despite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection.
In a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates were grouped into spoligotype families and lineages following previously published criteria. Time trends, HIV status, drug resistance and outcome were examined by spoligotype family and lineage. In addition, transmissibility was examined among pairs of cases with known epidemiological contact by assessing the proportion of transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity of the M tuberculosis strains. 760 spoligotypes were obtained from smears from 518 patients from 1986-2002, and 377 spoligotypes from cultures from 347 patients from 2005-2008. There was good consistency in patients with multiple specimens. Among 781 patients with first episode tuberculosis, the majority (76%) had Lineage 4 ("European/American") strains; 9% had Lineage 3 ("East-African/Indian"); 8% Lineage 1 ("Indo-Oceanic"); and 2% Lineage 2 ("East-Asian"); others unclassifiable. Over time the proportion of Lineage 4 decreased from >90% to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains were more common in those with HIV infection, even after adjusting for age, sex and year. There were no associations with drug resistance or outcome, and no differences by lineage in the proportion of pairs in which transmission was confirmed.
This is the first study to describe long term trends in the four M. tuberculosis lineages in a population. Lineage 4 has probably been longstanding in this population, with relatively recent introductions and spread of Lineages1-3, perhaps influenced by the HIV epidemic.
PLoS ONE 01/2010; 5(8):e12259. · 4.09 Impact Factor
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ABSTRACT: Our purpose was to elucidate the patterns and trends of autochthonous leprosy in Japan from 1964 to 2008, to compare them with the findings from other studies of leprosy in decline, and to determine whether M. leprae transmission persists in Japan.
Data on registered leprosy cases in Japan in the period 1964-2008 were analysed with reference to trends in case detection, geographical distribution, age at diagnosis, sex, classification, family history and broad correlation with socioeconomic conditions.
A consistent decline in leprosy case detection was observed in all areas of the country over the period 1964-2008. Highest incidence was consistently in Okinawa, the southernmost part of Japan. Autochthonous leprosy has not been reported in anyone born in Japan since 1980. Increasing average age and a shift towards lower latitudes were demonstrated throughout the period. There was an inverse association between regional measures of wealth and leprosy incidence.
Leprosy has declined throughout the past century in Japan. Autochthonous transmission has probably stopped in mainland Japan, but may still occur at a low level in Okinawa, the country's southernmost region. Analyses of data on autochthonous cases revealed patterns similar to those reported in other countries with declining leprosy. Detailed comparisons between countries with very low leprosy incidence may help us to better understand the epidemiology of leprosy.
Leprosy review 12/2009; 80(4):432-40. · 1.04 Impact Factor
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Paul E M Fine
The Journal of Infectious Diseases 10/2009; 200(5):673-5. · 6.41 Impact Factor
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ABSTRACT: Routine vaccination programmes have led to substantial declines in the incidence of most of the target diseases. In these circumstances, vaccine effects beyond those on the target diseases may become evident. Several studies have suggested that certain vaccines may influence mortality in low income settings in ways that cannot be attributed to effects on target diseases. Trials of such 'non-specific' effects are difficult if not impossible to organise; and observational studies of them are prone to serious confounding, because those who do or do not receive vaccines are likely to differ in many ways, some of which relate to their subsequent risk of early death, independent of vaccination. They are also prone to other biases, including the selective loss of vaccination records for children who die. We review these potential sources of bias and suggest what and how data may be collected to optimise the validity of such studies.
Trop Med Int Health. 09/2009; 14(9):969-76.
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Paul E M Fine,
Thomas N Williams,
Peter Aaby,
Karin Källander,
Lawrence H Moulton,
Katie L Flanagan,
Peter G Smith,
Christine S Benn,
Aaby P,
Adjuik M, [......],
Rodrigues L,
Rodrigues A,
Scott A,
Shann F,
Sie A,
Simondon KB,
Smith PG,
Welaga P,
Williams TN,
Yadav K
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ABSTRACT: Routine vaccination programmes have led to substantial declines in the incidence of most of the target diseases. In these circumstances, vaccine effects beyond those on the target diseases may become evident. Several studies have suggested that certain vaccines may influence mortality in low income settings in ways that cannot be attributed to effects on target diseases. Trials of such 'non-specific' effects are difficult if not impossible to organise; and observational studies of them are prone to serious confounding, because those who do or do not receive vaccines are likely to differ in many ways, some of which relate to their subsequent risk of early death, independent of vaccination. They are also prone to other biases, including the selective loss of vaccination records for children who die. We review these potential sources of bias and suggest what and how data may be collected to optimise the validity of such studies.
Tropical Medicine & International Health 07/2009; 14(9):969-76. · 2.80 Impact Factor
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Maeve K Lalor,
Anne Ben-Smith,
Patricia Gorak-Stolinska,
Rosemary E Weir,
Sian Floyd,
Rose Blitz,
Hazzie Mvula,
Melanie J Newport,
Keith Branson,
Nuala McGrath,
Amelia C Crampin, Paul E M Fine,
Hazel M Dockrell
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ABSTRACT: Bacille Calmette-Guérin (BCG) vaccination induces a marked increase in the interferon (IFN)-gamma response to Mycobacterium tuberculosis purified protein derivative (Mtb PPD) in UK adolescents, but not in Malawian adolescents. We hypothesized that Mtb PPD-induced IFN-gamma after BCG vaccination would be similar in infants from these 2 countries. Infants were vaccinated with BCG during the first 3-13 weeks of life. Three months after BCG vaccination, 51 (100%) of 51 UK infants had an IFN-gamma response to Mtb PPD, compared to 41 (53%) of 78 of Malawian infants, in whom responses varied according to their season of birth. We conclude that population differences in immune responses after BCG vaccination are observed among infants, as well as among young adults.
The Journal of Infectious Diseases 04/2009; 199(6):795-800. · 6.41 Impact Factor
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ABSTRACT: Tuberculosis (TB) patients with strains common to other recent cases ('clustering') suggest recent transmission. HIV status and age may affect proportions clustered. We investigated TB clustering by HIV and age in a population-based study in Malawi. Among 746 patients, HIV infection increased the proportion clustered. Sex-period-adjusted odds ratios for the association of HIV and clustering were 1.26 (95% CI 0.4-4.1) for ages 15-25 years, 1.40 (0.9-2.3) for 25-50 years and 10.44 (2.3-47.9) for >50 years and remained stable over two periods examined. These results suggest that HIV increases the proportion of TB due to recent transmission in the elderly.
Transactions of the Royal Society of Tropical Medicine and Hygiene 04/2009; 103(12):1187-9. · 2.16 Impact Factor
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ABSTRACT: To investigate individual, household and community factors associated with HIV test refusal in a counselling and testing programme offered at population level in rural Malawi.
HIV counselling and testing was offered to individuals aged 18-59 at their homes. Individual variables were collected by interviews and physical examinations. Household variables were determined as part of a previous census. Multivariate models allowing for household and community clustering were used to assess associations between HIV test refusal and explanatory variables.
Of 2303 eligible adults, 2129 were found and 1443 agreed to HIV testing. Test refusal was less likely by those who were never married [adjusted odds ratio (aOR) 0.50 for men (95% CI 0.32; 0.80) and 0.44 (0.21; 0.91) for women] and by farmers [aOR 0.70 (0.52; 0.96) for men and 0.59 (0.40; 0.87) for women]. A 10% increase in cluster refusal rates increased the odds of refusal by 1.48 (1.32; 1.66) in men and 1.68 (1.32; 2.12) in women. Women counsellors increased the odds of refusal by 1.39 (1.00; 1.92) in men. Predictors of HIV test refusal in women were refusal of the husband as head of household [aOR 15.08 (9.39; 24.21)] and living close to the main road [aOR 6.07 (1.76; 20.98)]. Common reasons for refusal were fear of testing positive, previous HIV test, knowledge of HIV serostatus and the need for more time to think.
Successful VCT strategies need to encourage couples counselling and should involve participation of men and communities.
Tropical Medicine & International Health 11/2008; 13(11):1341-50. · 2.80 Impact Factor
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ABSTRACT: Objective To investigate individual, household and community factors associated with HIV test refusal in a counselling and testing programme offered at population level in rural Malawi.Methods HIV counselling and testing was offered to individuals aged 18–59 at their homes. Individual variables were collected by interviews and physical examinations. Household variables were determined as part of a previous census. Multivariate models allowing for household and community clustering were used to assess associations between HIV test refusal and explanatory variables.Results Of 2303 eligible adults, 2129 were found and 1443 agreed to HIV testing. Test refusal was less likely by those who were never married [adjusted odds ratio (aOR) 0.50 for men (95% CI 0.32; 0.80) and 0.44 (0.21; 0.91) for women] and by farmers [aOR 0.70 (0.52; 0.96) for men and 0.59 (0.40; 0.87) for women]. A 10% increase in cluster refusal rates increased the odds of refusal by 1.48 (1.32; 1.66) in men and 1.68 (1.32; 2.12) in women. Women counsellors increased the odds of refusal by 1.39 (1.00; 1.92) in men. Predictors of HIV test refusal in women were refusal of the husband as head of household [aOR 15.08 (9.39; 24.21)] and living close to the main road [aOR 6.07 (1.76; 20.98)]. Common reasons for refusal were fear of testing positive, previous HIV test, knowledge of HIV serostatus and the need for more time to think.Conclusion Successful VCT strategies need to encourage couples counselling and should involve participation of men and communities.Objectif: Investiguer les facteurs individuels, familiaux et communautaires associés au refus du test de dépistage du VIH dans un programme de conseil et dépistage offert au niveau de la population dans les régions rurales au Malawi.Méthodes: Le conseil et dépistage volontaire du VIH a été proposé aux personnes âgées de 18 à 59 ans à leur domicile. Les variables individuelles ont été recueillies par des entretiens et des examens physiques. Les variables des ménages ont été déterminées dans le cadre d’un recensement précédent. Des modèles multivariés permettant le regroupement selon le ménage ou la communauté ont été utilisés pour évaluer les associations entre le refus du test VIH et des variables explicatives.Résultats: Sur 2303 adultes éligibles, 2129 ont été retrouvés et 1443 ont accepté le dépistage du VIH. Le refus du test était moins probable chez ceux qui n’avaient jamais été mariés (odds ratio ajusté (AOR) 0,50 (IC95%: 0,32 - 0,80) pour les hommes et 0,44 (0,21 - 0,91) pour les femmes) et chez les agriculteurs (AOR 0,70 (0,52- 0,96) pour les hommes et 0,59 (0,40 - 0,87) pour les femmes). Une augmentation de 10% dans le taux de refus de groupe augmentait les chances de refus de 1,48 (1,32 - 1,66) chez les hommes et 1,68 (1,32 - 2,12) chez les femmes. Les femmes conseillères augmentaient les chances de refus de 1,39 (1,00 - 1,92) chez les hommes. Les prédicteurs du refus du test VIH chez les femmes étaient le refus du mari en tant que chef de ménage (AOR 15,08 (9,39 - 24,21)) et la vie à proximité de la route principale (AOR 6,07 (1,76 - 20,98)). Les raisons courantes pour le refus étaient la peur d’un test positif, un précédent test de dépistage du VIH, la connaissance du statut sérologique VIH et le besoin de plus de temps pour y penser.Conclusion: La réussite des stratégies CDV nécessite un encouragement pour le conseil des couples et l’implication de la participation des hommes et des communautés.Objetivo: Investigar los factores individuales, del hogar y comunitarios asociados con la no aceptación del aconsejamiento y prueba para VIH en un programa ofrecido a nivel poblacional en Malawi rural.Métodos: Se ofreció aconsejamiento y prueba domiciliaria para VIH a individuos con edades comprendidas entre los 18-59 años. Las variables individuales fueron recolectadas mediante entrevistas y exámenes físicos. Las variables relacionadas con el hogar fueron determinadas a partir de un censo anterior. Se utilizaron modelos multivariados que permitieron hacer agrupaciones por hogar y comunidad, con el fin de evaluar las asociaciones entre el rechazo a la prueba de VIH y las variables explicativas.Resultados: De 2303 adultos elegibles, se encontraron 2129, y 1443 consintieron realizarse la prueba de VIH. Era menos probable que rechazasen la prueba aquellos que nunca habían estado casados (odds ratio ajustado (aOR) 0.50 para hombres (95% CI 0.32; 0.80) y 0.44 (0.21; 0.91) para mujeres) y los agricultores (aOR 0.70 (0.52; 0.96) para hombres y 0.59 (0.40; 0.87) para mujeres). Un aumento del 10% de la tasa de rechazo en grupo aumentó la probabilidad de rechazo en 1.48 (1.32; 1.66) para hombres y 1.68 (1.32; 2.12) para mujeres. El que el consejero fuese una mujer aumentaba el la probabilidad de rechazo en 1.39 (1.00; 1.92) para los hombres. Vaticinadores del rechazo de la prueba entre mujeres eran el que su marido – como cabeza de familia – la hubiese rechazado (aOR 15.08 (9.39; 24.21)) y el vivir cerca de una calle principal (aOR 6.07 (1.76; 20.98)). Razones comunes para rechazar la prueba eran el miedo a ser positivos, haber realizado previamente una prueba de VIH, conocimiento del estatus serológico para VIH y la necesidad de más tiempo para pensárselo.Conclusión: Para una estrategia exitosa de aconsejamiento y prueba voluntaria, es necesario fomentar el aconsejamiento de parejas y debería involucrar la participación de los hombres y las comunidades.
Tropical Medicine & International Health 10/2008; 13(11):1341 - 1350. · 2.80 Impact Factor
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ABSTRACT: Tuberculosis patients with identical strains of Mycobacterium tuberculosis are described as clustered. Cluster size may depend on patient or strain characteristics. In a 7-year population-based study of tuberculosis in Karonga District, Malawi, clusters were defined by using IS6110 restriction fragment length polymorphism, excluding patterns with <5 bands. Spoligotyping was used to compare strains with an international database. Among 682 clustered patients, cluster size ranged from 2 to 37. Male patients, young adults, and town residents were over-represented in large clusters. Cluster size was not associated with HIV status or death from tuberculosis. Spoligotypes from 9 (90%) of 10 large cluster strains were identical or very similar (1 spacer different) to common spoligotypes found elsewhere, compared with 37 (66%) of 56 of those from nonclustered patients (p = 0.3). Large clusters were associated with factors likely to be related to social mixing, but spoligotypes of common strains in this setting were also common types elsewhere, consistent with strain differences in transmissibility.
Emerging Infectious Diseases 07/2008; 14(7):1060-6. · 6.79 Impact Factor
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Andreas Jahn,
Sian Floyd,
Amelia C Crampin,
Frank Mwaungulu,
Hazzie Mvula,
Fipson Munthali,
Nuala McGrath,
Johnbosco Mwafilaso,
Venance Mwinuka,
Bernard Mangongo, Paul E M Fine,
Basia Zaba,
Judith R Glynn
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ABSTRACT: Malawi, which has about 80,000 deaths from AIDS every year, made free antiretroviral therapy available to more than 80 000 patients between 2004 and 2006. We aimed to investigate mortality in a population before and after the introduction of free antiretroviral therapy, and therefore to assess the effects of such programmes on survival at the population level.
We used a demographic surveillance system to measure mortality in a population of 32,000 in northern Malawi, from August, 2002, when free antiretroviral therapy was not available in the study district, until February, 2006, 8 months after a clinic opened. Causes of death were established through verbal autopsies (retrospective interviews). Patients who registered for antiretroviral therapy at the clinic were identified and linked to the population under surveillance. Trends in mortality were analysed by age, sex, cause of death, and zone of residence.
Before antiretroviral therapy became available in June, 2005, mortality in adults (aged 15-59 years) was 9.8 deaths for 1000 person-years of observation (95% CI 8.9-10.9). The probability of dying between the ages of 15 and 60 years was 43% (39-49) for men and 43% (38-47) for women; 229 of 352 deaths (65.1%) were attributed to AIDS. 8 months after the clinic that provided antiretroviral therapy opened, 107 adults from the study population had accessed treatment, out of an estimated 334 in need of treatment. Overall mortality in adults had decreased by 10% from 10.2 to 8.7 deaths for 1000 person-years of observation (adjusted rate ratio 0.90, 95% CI 0.70-1.14). Mortality was reduced by 35% (adjusted rate ratio 0.65, 0.46-0.92) in adults near the main road, where mortality before antiretroviral therapy was highest (from 13.2 to 8.5 deaths per 1000 person-years of observation before and after antiretroviral therapy). Mortality in adults aged 60 years or older did not change.
Our findings of a reduction in mortality in adults aged between 15 and 59 years, with no change in those older than 60 years, suggests that deaths from AIDS were averted by the rapid scale-up of free antiretroviral therapy in rural Malawi, which led to a decline in adult mortality that was detectable at the population level.
The Lancet 06/2008; 371(9624):1603-11. · 38.28 Impact Factor
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ABSTRACT: To assess the social and economic impact of HIV-related illness and death on the spouses of HIV-infected individuals.
From population-based surveys in the 1980s in Karonga district, northern Malawi, 197 'index individuals' were identified as HIV-positive. A total of 396 HIV-negative 'index individuals' were selected as a comparison group. These individuals, and their spouses and children, were followed up in 1998-2000, in a retrospective cohort study. All analyses compared spouses of HIV-positive indexes with those of HIV-negative indexes.
By 1998-2000, most marriages involving an HIV-positive index individual had ended in widowhood. Twenty-Six percent of the wives of HIV-positive index men experienced household dissolution precipitated by widowhood, compared with 5% of the wives of HIV-negative index men. Corresponding percentages for husbands of index women were 14% and 1%. Widow inheritance was uncommon. The remarriage rate among separated or widowed wives of HIV-positive index men was half that of such wives of HIV-negative index men. About 30% of surviving wives of HIV-positive index men were household heads at the time of follow-up, compared with 5% of such wives of HIV-negative index men. Almost all these women were widows who lost their husband when >35 years old, and they had relatively few household assets.
The social and economic impact of HIV on the spouses of HIV-infected individuals in rural northern Malawi is substantial. Interventions that strengthen society's ability to absorb and support widows and widowers, and their dependents, without necessarily involving the traditional coping mechanism of remarriage, are essential.
Tropical Medicine & International Health 05/2008; 13(4):520-31. · 2.80 Impact Factor
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ABSTRACT: Inadequate understanding of the transmission of Mycobacterium leprae makes it difficult to predict the impact of leprosy control interventions. Genotypic tests that allow tracking of individual bacterial strains would strengthen epidemiological studies and contribute to our understanding of the disease.
Genotyping assays based on variation in the copy number of short tandem repeat sequences were applied to biopsies collected in population-based epidemiological studies of leprosy in northern Malawi, and from members of multi-case households in Hyderabad, India. In the Malawi series, considerable genotypic variability was observed between patients, and also within patients, when isolates were collected at different times or from different tissues. Less within-patient variability was observed when isolates were collected from similar tissues at the same time. Less genotypic variability was noted amongst the closely related Indian patients than in the Malawi series.
Lineages of M. leprae undergo changes in their pattern of short tandem repeat sequences over time. Genetic divergence is particularly likely between bacilli inhabiting different (e.g., skin and nerve) tissues. Such variability makes short tandem repeat sequences unsuitable as a general tool for population-based strain typing of M. leprae, or for distinguishing relapse from reinfection. Careful use of these markers may provide insights into the development of disease within individuals and for tracking of short transmission chains.
PLoS Neglected Tropical Diseases 02/2008; 2(4):e214. · 4.69 Impact Factor
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Rosemary E Weir, Paul E M Fine,
Sian Floyd,
Sally Stenson,
Carolynne Stanley,
Keith Branson,
Warwick J Britton,
Kris Huygen,
Mahavir Singh,
Gillian Black,
Hazel M Dockrell
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ABSTRACT: An increase in interferon-gamma (IFN-gamma) production to Mycobacterium tuberculosis purified protein derivative (Mtb PPD), as measured in the cultured diluted whole blood assay, is one indicator of a protective immune response to BCG vaccine. We have explored the potential for this assay to be improved by measuring IFN-gamma responses to more defined antigens of M. tuberculosis (short-term and mid-term culture filtrates, ESAT-6, 38 kDa), Mycobacterium bovis (MPB70), M. bovis BCG (Antigen 85) and Mycobacterium leprae (35 kDa), in UK teenagers before and 1 year after BCG vaccination (or no vaccination as controls). There was a significant increase in response to the culture filtrates post-vaccination, but this was no greater than that to Mtb PPD. Many teenagers responded to the purified antigens, in particular to Antigen 85, prior to vaccination, and BCG vaccination could only augment this pre-existing response to a limited extent; prior exposure to environmental mycobacteria can thus induce cross-reactive responses to antigens which complicate interpretation of in vitro assays of vaccine response. In contrast, ESAT-6 was recognised by only one teenager prior to vaccination, and, as expected, responses were not boosted by BCG. We therefore conclude that Mtb PPD is the antigen preparation of choice for assessing the immunogenicity of BCG vaccination.
Tuberculosis 02/2008; 88(1):31-8. · 3.47 Impact Factor
