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Biomedical subjects

Daniel Chandramohan

Publications and source records attributed to Daniel Chandramohan.

16 recordsLinked to original sources
PubMed2006

Over-diagnosis of malaria is not a lost cause.

BACKGROUND: Recent studies have highlighted the over-diagnosis of malaria in clinical settings in Africa. This study assessed the impact of a training programme implemented as part of an intervention trial on diagnostic behaviour of clinicians in a rural district hospital in a low-moderate malaria transmission setting. METHODS: From the beginning of 2005, a randomized controlled trial (RCT) of intermittent preventive treatment for malaria in infants (IPTi) has been conducted at the study hospital. As part of the RCT, the study team offered laboratory quality assurance, and supervision and training of paediatric ward staff using information on malaria epidemiology in the community. Data on clinical and blood slide confirmed cases of malaria from 2001 to 2005 were extracted from the hospital records. RESULTS: The proportion of blood slides positive for malaria parasites had decreased from 21% in 2001 to 7% in 2005 (p < .01). The proportion of outpatient and inpatient cases diagnosed as malaria ranged between 34% and 28% from 2001 to 2004 and this decreased substantially to 17% after the introduction of the package of training and support in 2005 (p < .01). There was no clear trend in the ratio of blood slide examined versus total diagnosis of malaria. CONCLUSION: It may be possible to change the diagnostic behaviour of clinicians by rigorous training using local malaria epidemiology data and supportive supervision.

Clinical Laboratory Techniques↗
PubMed2006

Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial.

BACKGROUND: The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens. METHODS: Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen on days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703. FINDINGS: PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often on day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison). INTERPRETATION: Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.

Adult↗
PubMed2006

Verbal autopsy: current practices and challenges.

Cause-of-death data derived from verbal autopsy (VA) are increasingly used for health planning, priority setting, monitoring and evaluation in countries with incomplete or no vital registration systems. In some regions of the world it is the only method available to obtain estimates on the distribution of causes of death. Currently, the VA method is routinely used at over 35 sites, mainly in Africa and Asia. In this paper, we present an overview of the VA process and the results of a review of VA tools and operating procedures used at demographic surveillance sites and sample vital registration systems. We asked for information from 36 field sites about field-operating procedures and reviewed 18 verbal autopsy questionnaires and 10 cause-of-death lists used in 13 countries. The format and content of VA questionnaires, field-operating procedures, cause-of-death lists and the procedures to derive causes of death from VA process varied substantially among sites. We discuss the consequences of using varied methods and conclude that the VA tools and procedures must be standardized and reliable in order to make accurate national and international comparisons of VA data. We also highlight further steps needed in the development of a standard VA process.

Autopsy↗
PubMed2006

Validity of verbal autopsy procedures for determining cause of death in Tanzania.

OBJECTIVES: To validate verbal autopsy (VA) procedures for use in sample vital registration. Verbal autopsy is an important method for deriving cause-specific mortality estimates where disease burdens are greatest and routine cause-specific mortality data do not exist. METHODS: Verbal autopsies and medical records (MR) were collected for 3123 deaths in the perinatal/neonatal period, post-neonatal <5 age group, and for ages of 5 years and over in Tanzania. Causes of death were assigned by physician panels using the International Classification of Disease, revision 10. Validity was measured by: cause-specific mortality fractions (CSMF); sensitivity; specificity and positive predictive value. Medical record diagnoses were scored for degree of uncertainty, and sensitivity and specificity adjusted. Criteria for evaluating VA performance in generating true proportional mortality were applied. RESULTS: Verbal autopsy produced accurate CSMFs for nine causes in different age groups: birth asphyxia; intrauterine complications; pneumonia; HIV/AIDS; malaria (adults); tuberculosis; cerebrovascular diseases; injuries and direct maternal causes. Results for 20 other causes approached the threshold for good performance. CONCLUSIONS: Verbal autopsy reliably estimated CSMFs for diseases of public health importance in all age groups. Further validation is needed to assess reasons for lack of positive results for some conditions.

Adolescent↗
PubMed2006

Core verbal autopsy procedures with comparative validation results from two countries.

BACKGROUND: Cause-specific mortality statistics remain scarce for the majority of low-income countries, where the highest disease burdens are experienced. Neither facility-based information systems nor vital registration provide adequate or representative data. The expansion of sample vital registration with verbal autopsy procedures represents the most promising interim solution for this problem. The development and validation of core verbal autopsy forms and suitable coding and tabulation procedures are an essential first step to extending the benefits of this method. METHODS AND FINDINGS: Core forms for peri- and neonatal, child, and adult deaths were developed and revised over 12 y through a project of the Tanzanian Ministry of Health and were applied to over 50,000 deaths. The contents of the core forms draw upon and are generally comparable with previously proposed verbal autopsy procedures. The core forms and coding procedures based on the International Statistical Classification of Diseases (ICD) were further adapted for use in China. These forms, the ICD tabulation list, the summary validation protocol, and the summary validation results from Tanzania and China are presented here. CONCLUSIONS: The procedures are capable of providing reasonable mortality estimates as adjudged against stated performance criteria for several common causes of death in two countries with radically different cause structures of mortality. However, the specific causes for which the procedures perform well varied between the two settings because of differences in the underlying prevalence of the main causes of death. These differences serve to emphasize the need to undertake validation studies of verbal autopsy procedures when they are applied in new epidemiological settings.

Adult↗
PubMed2005

Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana.

OBJECTIVE: To evaluate the effects of intermittent preventive treatment for malaria in infants (IPTi) with sulfadoxine-pyrimethamine in an area of intense, seasonal transmission. DESIGN: Cluster randomised placebo controlled trial, with 96 clusters allocated randomly to sulfadoxine-pyrimethamine or placebo in blocks of eight. INTERVENTIONS: Children received sulfadoxine-pyrimethamine or placebo and one month of iron supplementation when they received DPT-2, DPT-3, or measles vaccinations and at 12 months of age. MAIN OUTCOME MEASURES: Incidence of malaria and of anaemia determined through passive case detection. RESULTS: 89% (1103/1242) of children in the placebo group and 88% (1088/1243) in the IPTi group completed follow-up to 24 months of age. The protective efficacy of IPTi against all episodes of malaria was 24.8% (95% confidence interval 14.3% to 34.0%) up to 15 months of age. IPTi had no protective effect against malaria between 16 and 24 months of age (protective efficacy -4.9%, -21.3% to 9.3%). The incidence of high parasite density malaria (> or = 5000 parasites/mul) was higher in the IPTi group than in the placebo group between 16 and 24 months of age (protective efficacy -19.5%, -39.8% to -2.2%). IPTi reduced hospital admissions with anaemia by 35.1% (10.5% to 52.9%) up to 15 months of age. IPTi had no significant effect on anaemia between 16 and 24 months of age (protective efficacy -6.4%, -76.8% to 35.9%). The relative risk of death up to 15 months of age in the IPTi group was 1.26 (95% confidence interval 0.81 to 1.96; P = 0.31), and from 16 to 24 months it was 1.28 (0.77 to 2.14; P = 0.35). CONCLUSIONS: Intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine can reduce malaria and anaemia in infants even in seasonal, high transmission areas, but concern exists about possible rebound in the incidence of malaria in the second year of life.

Anemia↗
PubMed2005

Community-based surveillance: a pilot study from rural Cambodia.

OBJECTIVE: This study seeks to assess the performance of a community-based surveillance system (CBSS), developed and implemented in seven rural communes in Cambodia from 2000 to 2002 to provide timely and representative information on major health problems and life events, and so permit rapid and effective control of outbreaks and communicable diseases in general. METHODS: Lay people were trained as Village Health Volunteers (VHVs) to report suspected outbreaks, important infectious diseases, and vital events occurring in their communities to local health staff who analysed the data and gave feedback to the volunteers during their monthly meetings. RESULTS: Over 2 years of its implementation, the system was able to detect outbreaks early, regularly monitor communicable disease trends, and to provide continuously updated information on pregnancies, births and deaths in the rural areas. In addition, the system triggered effective responses from both health staff and VHVs for disease control and prevention and in outbreaks. CONCLUSION: A CBSS can successfully fill the gaps of the current health facility-based disease surveillance system in the rapid detection of outbreaks, in the effective monitoring of communicable diseases, and in the notification of vital events in rural Cambodia. Its replication or adaptation for use in other rural areas in Cambodia and in other developing countries is likely to be beneficial and cost-effective.

Acute Disease↗
PubMed2003

Antifolate antimalarial resistance in southeast Africa: a population-based analysis.

BACKGROUND: Sulfadoxine-pyrimethamine was first introduced for treatment of malaria in Africa during the early 1980s for cases when chloroquine treatment failed, and has since become the first-line treatment in many countries. Resistance to sulfadoxine-pyrimethamine is now increasing, especially in southeast Africa. METHODS: We characterised genetic change in dhfr and dhps genes in the Plasmodium falciparum population of KwaZulu-Natal, South Africa, during 1995-99, a period of rapid deterioration of the effectiveness of sulfadoxine-pyrimethamine. We assessed the evolutionary origin of the resistance by analysing polymorphic microsatellite repeats in the flanking region of the dhfr and dhps genes, which show whether resistance alleles originated through shared or independent ancestral mutation events. We then assessed the current extent of dispersal of dhfr and dhps resistance alleles by doing the same analysis in P falciparum sampled from communities in the Kilimanjaro region of northern Tanzania in 2001. FINDINGS: The large genetic change during 1995-99 in KwaZulu-Natal, South Africa, in both the health facility and the wider community surveys, was at the dhps locus, apparently because resistance at dhfr was established before 1995. The allelic determinants of resistance in this province share a common evolutionary origin with those found in Kilimanjaro, Tanzania, even though the two sites are 4000 km apart. INTERPRETATION: Three resistant dhfr alleles, and one resistant dhps allele, each derived from independent ancestral lineages, have been driven through through southeast Africa. The movement by the dhfr alleles (pyrimethamine resistance) preceded that of the dhps allele (sulfadoxine resistance). Our findings emphasise that gene flow rather than new mutations has been the most common originator of resistance in African countries.

Adult↗
PubMed2003

A health facility based case-control study of effectiveness of insecticide treated nets: potential for selection bias due to pre-treatment with chloroquine.

Case control studies offer an attractive way to assess the effectiveness of insecticide treated nets (ITN) under programme conditions but have the drawback of being susceptible to bias in the choice of controls. We evaluated the potential for pre-treatment with chloroquine to result in misclassification of cases and controls and affect estimates of ITN effectiveness in case control studies in urban and rural clinics in Eastern Afghanistan. During the one-month study, use of ITN showed no effect against malaria in the urban clinic (adjusted odds ratio OR 1.08; 95% CI 0.73-1.6) and the protective effect seen in the rural clinic was not significant (OR 0.62; 95% CI 0.2-2.4). Levels of pre-treatment were high in both clinics: 24% in urban and 19% in rural clinic attenders. In the urban clinic attenders the level of pre-treatment between bed net users and non-users was not significantly different (OR 1.07, 95% CI 0.70-1.64); therefore the misclassification of cases as controls did not introduce any selection bias. Amongst rural clinic attenders, bed net users were less likely to pre-treat with chloroquine than users (OR 0.33, 95% CI 0.14-0.77); this introduced a selection bias that resulted in an underestimation of the effectiveness of bed nets. Case control studies using health facility data are liable to selection bias especially in areas of high pre-treatment rates with chloroquine. Generalisation of results over a wide geographic region, or between urban and rural settings, may not be appropriate.

Adolescent↗
PubMed2003

Socio-economic factors associated with the purchasing of insecticide-treated nets in Afghanistan and their implications for social marketing.

Malaria is often a major health problem in war-torn countries in the tropics owing to the collapse of health services and the vulnerability of displaced populations to epidemics. Insecticide-treated nets (ITN) represent one of the few options for obtaining protection against malaria in unstable settings deficient in health infrastructure. Social marketing of subsidized ITN by a consortium of non-governmental organizations began in Afghanistan in 1993 and has continued every year since then despite regular political turmoil. Almost 350,000 nets have been sold and approximately 1.2 million people protected. In 2000 we examined the determinants of ITN purchasing among households in Nangarhar province, eastern Afghanistan, as part of an effort to increase ITN uptake. The survey was conducted using a structured questionnaire to collect data on socio-economic characteristics and malaria beliefs and practices among more than 400 net-owning and non-net-owning households. A composite socio-economic index was created using principal components analysis, and survey households were divided into socio-economic quartiles. ITN were 4.5 times more likely to be purchased by families from the richest quartile and 2.3 times more likely to be purchased from the upper-middle quartile than from the two lower quartiles. Even so, a significant minority from the lower quartiles did prioritize and buy ITN. In conflict affected countries where livelihoods are compromised, it is necessary to target subsidies at the most impoverished to make ITN affordable and to improve overall coverage.

Adult↗
PubMed2003

Molecular determination of point mutation haplotypes in the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum in three districts of northern Tanzania.

The antimalarial combination of sulfadoxine and pyrimethamine (SP) was introduced as first-line treatment for uncomplicated malaria in Tanzania during 2001 following 18 years of second-line use. The genetic determinants of in vitro resistance to the two drugs individually are shown to be point mutations at seven sites in the dihydrofolate reductase gene (dhfr) conferring resistance to pyrimethamine and five sites in the dihydropteroate synthase (dhps) gene conferring resistance to sulfadoxine. Different combinations of mutations within each gene confer differing degrees of insensitivity, but information about the frequency with which allelic haplotypes occur has been lacking because of the complicating effects of multiple infection. Here we used a novel high-throughput sequence-specific oligonucleotide probe-based approach to examine the present resistance status of three Plasmodium falciparum populations in northern Tanzania. By using surveys of asymptomatic infections and screening for the presence of all known point mutations in dhfr and dhps genes, we showed that just five dhfr and three dhps allelic haplotypes are present. High frequencies of both triple-mutant dhfr and double-mutant dhps mutant alleles were found in addition to significant interregional heterogeneity in allele frequency. In vivo studies have shown that the cooccurrence of three dhfr mutations and two dhps mutations in an infection prior to treatment is statistically predictive of treatment failure. We have combined data for both loci to determine the frequency of two-locus genotypes. The triple-dhfr/double-dhps genotype is present in all three regions with frequencies ranging between 30 and 63%, indicating that treatment failure rates are likely to be high.

Alleles↗
PubMed2002

Use of clinical algorithms for diagnosing malaria.

Several attempts have been made to identify symptoms and signs based algorithms for diagnosing malaria. In this paper, we review the results of published studies and assess the risks and benefits of this approach in different epidemiological settings. Although in areas with a low prevalence the risk of failure to treat malaria resulting from the use of algorithms was low, the reduction in the wastage of drugs was trivial. The odds of wastage of drugs increased by 1.49 (95% confidence limit 1.45-1.51) for each 10% decrease in the prevalence of malaria. In highly endemic areas the algorithms had a high risk of failure to treat malaria. The odds of failure to treat increased by 1.57 (95% confidence limit 1.50-1.65) for each 10% increase in the prevalence. Furthermore, the best clinical algorithms for diagnosing malaria were site-specific. We conclude that the accuracy of clinical algorithms for diagnosing malaria is not sufficient to determine whether antimalarial drugs should be given to children presenting with febrile illness. In highly endemic areas where laboratory support is not available, the policy of offering antimalarial drugs to all children presenting with a febrile illness recommended by the integrated child management initiative is appropriate.

Algorithms↗
PubMed2002

Unstable malaria transmission and maternal mortality--experiences from Rwanda.

Data on malaria in pregnancy in unstable transmission areas are scarce. We investigated malaria in pregnancy at Byumba District Hospital, Rwanda, over 3 years (January 1997-December 1999). Byumba, at an altitude of 2300 m, has low levels of malaria transmission. A malaria epidemic in February 1998 led to a fourfold increase in malaria admissions among pregnant women and to a fivefold increase in maternal deaths because of malaria. Safe Motherhood programmes should note that even in non-epidemic years malaria can cause a large proportion of maternal deaths, and that national and international responses to malaria in pregnancy need strengthening.

Adolescent↗
PubMed2002

Prevention of malaria in Afghanistan through social marketing of insecticide-treated nets: evaluation of coverage and effectiveness by cross-sectional surveys and passive surveillance.

Malaria is often a major health problem in countries undergoing war or conflict owing to breakdown of health systems, displacement of vulnerable populations, and the increased risk of epidemics. After 23 years of conflict, malaria has become prevalent in many rural areas of Afghanistan. From 1993 to the present, a network of non-governmental organizations, co-ordinated by HealthNet International, has operated a programme of bednet sales and re-treatment in lowland areas. To examine whether a strategy based on insecticide-treated nets (ITN) is a viable public health solution to malaria, communities were given the opportunity to buy nets and then monitored to determine population coverage and disease control impact. This was carried out using two contrasting methods: cross-sectional surveys and passive surveillance from clinics using a case-control design. Nets were purchased by 59% of families. Cross-sectional surveys demonstrated a 59% reduction in the risk of Plasmodium falciparum infection among ITN users compared with non-users (OR 0.41; 95% CI 0.25-0.66). The passive surveillance method showed a comparable reduction in the risk of symptomatic P. falciparum malaria among ITN users (OR 0.31; 95% CI 0.21-0.47). The cross-sectional method showed a 50% reduction in risk of P. vivax infection in ITN users compared with non-users (OR 0.50; 95% CI 0.17-1.49) but this effect was not statistically significant. The passive surveillance method showed a 25% reduction in the risk of symptomatic P. vivax malaria (OR 0.75; 95% CI 0.66-0.85). ITN appeared to be less effective against P. vivax because of relapsing infections; hence an effect took more than one season to become apparent. Passive surveillance was cheaper to perform and gave results consistent with cross-sectional surveys. Untreated nets provided some protection. Data on socioeconomic status, a potential confounding factor, was not collected. However, at the time of net sales, there was no difference in malaria prevalence between buyers and non-buyers. The abundance of Anopheles stephensi, the main vector, did not appear to be affected by ITN. ITN constitute one of the few feasible options for protection against malaria in chronic emergencies.

Adolescent↗
PubMed2002

Characteristics of severe anemia and its association with malaria in young children of the Kassena-Nankana District of northern Ghana.

Severe anemia is thought to be the principal underlying cause of malaria death in areas of intense seasonal malaria transmission such as the Kassena-Nankana District of northern Ghana. Factors associated with severe anemia in young children, 6-24 months old, were elucidated by analyzing results of 2 malaria-associated anemia surveys (1996, 2000), separated by 4 years, but conducted in the same community and at the same seasonal time point. Age-adjusted comparison confirmed that the proportion of severely anemic children and overall mean hemoglobin (Hb) levels in the November 2000 sample were significantly improved over those of the 1996 sample (17.5 versus 26.4%, P = 0.03; Hb 7.5 versus 6.9 g/dL, P = 0.002). Weight-for-age Z-scores also indicated a significant improvement in the 2000 sample (-1.93 versus -2.20, P < 0.05). Independently, each survey identified statistically significant associations between severe anemia and age, parasite rate, fever, and sex. Relative to children with Hb > or = 6.0 g/dL, those with severe anemia (Hb < 6.0 g/dL) were older, more frequently parasitemic (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.08-2.35), more often febrile (OR, 2.44; 95% CI, 1.71-3.48), and predominantly male (OR, 1.50; 95% CI, 1.05-2.13). An association was identified in both surveys between severe anemia and residence in the northern part of the district, but no clear link was observed in relation to irrigation. Blood transfusions, a likely surrogate index of severe anemia in young children, followed a distinct seasonal pattern. Evidence suggests that dramatic peaks and troughs of severe anemia are regular and possibly predictable events that may be used to gauge the health and survival of young children in this area.

Anemia↗