Journal Article > ResearchFull Text
Glob Health Action. 1 February 2018; Volume 11 (Issue 1); DOI:10.1080/16549716.2018.1445467
Sagili KD, Satyanarayana S, Chadha SS, Wilson NC, Kumar AMV, et al.
Glob Health Action. 1 February 2018; Volume 11 (Issue 1); DOI:10.1080/16549716.2018.1445467
BACKGROUND:
The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices.
OBJECTIVES:
To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice.
METHODS:
From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes.
RESULTS:
In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice.
CONCLUSIONS:
OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.
The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices.
OBJECTIVES:
To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice.
METHODS:
From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes.
RESULTS:
In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice.
CONCLUSIONS:
OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 June 2004; Volume 9 (Issue 6); DOI:10.1111/j.1365-3156.2004.01249.x
van den Broek IVF, van der Wardt S, Talukder L, Chakma S, Brockman A, et al.
Trop Med Int Health. 1 June 2004; Volume 9 (Issue 6); DOI:10.1111/j.1365-3156.2004.01249.x
OBJECTIVE: To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh. METHODS: A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps). RESULTS: Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. Recurring parasitaemia was related to age (chi(2) = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). PCR analysis showed that some of these cases were novel infections. The adjusted recrudescence rate was 12.9% (95% CI 8.1-17.7) overall, and 16.6% (95% CI 3.5-29.7), 15.5% (95% CI 8.3-22.7) and 6.9% (95% CI 0.4-13.4) in three age groups (<5 years, 5-14, > or =15). The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced. CONCLUSIONS: The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh.
Journal Article > CommentaryFull Text
Public Health Action. 21 June 2014; Volume 4 (Issue 2); DOI:10.5588/pha.14.0012
Kumar AMV, Satyanarayana S, Wilson N, Chadha SS, Gupta D, et al.
Public Health Action. 21 June 2014; Volume 4 (Issue 2); DOI:10.5588/pha.14.0012
Journal Article > ResearchFull Text
J Infect Dis. 1 April 2007; Volume 195 (Issue 7); DOI:10.1086/512241
Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JH, et al.
J Infect Dis. 1 April 2007; Volume 195 (Issue 7); DOI:10.1086/512241
BACKGROUND: Relapses originating from hypnozoites are characteristic of Plasmodium vivax infections. Thus, reappearance of parasitemia after treatment can result from relapse, recrudescence, or reinfection. It has been assumed that parasites causing relapse would be a subset of the parasites that caused the primary infection. METHODS: Paired samples were collected before initiation of antimalarial treatment and at recurrence of parasitemia from 149 patients with vivax malaria in Thailand (n=36), where reinfection could be excluded, and during field studies in Myanmar (n=75) and India (n=38). RESULTS: Combined genetic data from 2 genotyping approaches showed that novel P. vivax populations were present in the majority of patients with recurrent infection (107 [72%] of 149 patients overall [78% of patients in Thailand, 75% of patients in Myanmar {Burma}, and 63% of patients in India]). In 61% of the Thai and Burmese patients and in 55% of the Indian patients, the recurrent infections contained none of the parasite genotypes that caused the acute infection. CONCLUSIONS: The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria.
Journal Article > ResearchFull Text
PLOS One. 5 December 2012; Volume 7 (Issue 12); DOI:10.1371/journal.pone.0051038
Kumar AMV, Satyanarayana S, Dewan P, Nair SA, Khaparde K, et al.
PLOS One. 5 December 2012; Volume 7 (Issue 12); DOI:10.1371/journal.pone.0051038
Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely.
Journal Article > ResearchFull Text
Mol Biol Evol. 1 December 2005; Volume 22 (Issue 12); DOI:10.1093/molbev/msi235
Anderson TJC, Nair SA, Sudimack D, Williams JT, Mayxay M, et al.
Mol Biol Evol. 1 December 2005; Volume 22 (Issue 12); DOI:10.1093/molbev/msi235
Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18-0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral expectations based on observed F(ST) values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach.
Journal Article > ResearchFull Text
PLOS One. 16 December 2013; Volume 8 (Issue 12); e84255.; DOI:10.1371/journal.pone.0084255
Bhat PG, Kumar AMV, Naik B, Satyanarayana S, KG D, et al.
PLOS One. 16 December 2013; Volume 8 (Issue 12); e84255.; DOI:10.1371/journal.pone.0084255
BACKGROUND
Severe acute malnutrition (SAM) is the most serious form of malnutrition affecting children under-five and is associated with many infectious diseases including Tuberculosis (TB). In India, nutritional rehabilitation centres (NRCs) have been recently established for the management of SAM including TB. The National TB Programme (NTP) in India has introduced a revised algorithm for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these guidelines in diagnosing TB among SAM children.
METHODS
A cross-sectional study involving review of records of all SAM children identified by health workers during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of Karnataka, India.
RESULTS
Of 1927 identified SAM children, 1632 (85%) reached NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB. Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not evaluated as per algorithm, tuberculin skin test alone was conducted in 307 (41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%). The yield of TB was higher among children evaluated as per algorithm (4%) as compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several operational challenges including non-availability of a full-time paediatrician, non-functioning X-ray machine due to frequent power cuts, use of tuberculin with suboptimal strength and difficulties in adhering to a complex diagnostic algorithm were observed.
CONCLUSION
This study showed that TB screening in NRCs was sub-optimal in Karnataka. Some children did not reach the NRC, while many of those who did were either not or sub-optimally evaluated for TB. This study pointed to a number of operational issues that need to be addressed if this collaborative strategy is to identify more TB cases amongst malnourished children in India.
Severe acute malnutrition (SAM) is the most serious form of malnutrition affecting children under-five and is associated with many infectious diseases including Tuberculosis (TB). In India, nutritional rehabilitation centres (NRCs) have been recently established for the management of SAM including TB. The National TB Programme (NTP) in India has introduced a revised algorithm for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these guidelines in diagnosing TB among SAM children.
METHODS
A cross-sectional study involving review of records of all SAM children identified by health workers during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of Karnataka, India.
RESULTS
Of 1927 identified SAM children, 1632 (85%) reached NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB. Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not evaluated as per algorithm, tuberculin skin test alone was conducted in 307 (41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%). The yield of TB was higher among children evaluated as per algorithm (4%) as compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several operational challenges including non-availability of a full-time paediatrician, non-functioning X-ray machine due to frequent power cuts, use of tuberculin with suboptimal strength and difficulties in adhering to a complex diagnostic algorithm were observed.
CONCLUSION
This study showed that TB screening in NRCs was sub-optimal in Karnataka. Some children did not reach the NRC, while many of those who did were either not or sub-optimally evaluated for TB. This study pointed to a number of operational issues that need to be addressed if this collaborative strategy is to identify more TB cases amongst malnourished children in India.
Journal Article > ResearchFull Text
Proc Biol Sci. 2 June 2005; Volume 272 (Issue 1568); 1153-1161.; DOI:10.1098/rspb.2004.3026
Nash D, Nair SA, Mayxay M, Newton PN, Guthmann JP, et al.
Proc Biol Sci. 2 June 2005; Volume 272 (Issue 1568); 1153-1161.; DOI:10.1098/rspb.2004.3026
Neutral mutations may hitchhike to high frequency when they are situated close to sites under positive selection, generating local reductions in genetic diversity. This process is thought to be an important determinant of levels of genomic variation in natural populations. The size of genome regions affected by genetic hitchhiking is expected to be dependent on the strength of selection, but there is little empirical data supporting this prediction. Here, we compare microsatellite variation around two drug resistance genes (chloroquine resistance transporter (pfcrt), chromosome 7, and dihydrofolate reductase (dhfr), chromosome 4) in malaria parasite populations exposed to strong (Thailand) or weak selection (Laos) by anti-malarial drugs. In each population, we examined the point mutations underlying resistance and length variation at 22 (chromosome 4) or 25 (chromosome 7) microsatellite markers across these chromosomes. All parasites from Thailand carried the K76T mutation in pfcrt conferring resistance to chloroquine (CQ) and 2-4 mutations in dhfr conferring resistance to pyrimethamine. By contrast, we found both wild-type and resistant alleles at both genes in Laos. There were dramatic differences in the extent of hitchhiking in the two countries. The size of genome regions affected was smaller in Laos than in Thailand. We observed significant reduction in variation relative to sensitive parasites for 34-64 kb (2-4 cM) in Laos on chromosome 4, compared with 98-137 kb (6-8 cM) in Thailand. Similarly, on chromosome 7, we observed reduced variation for 34-69 kb (2-4 cM) around pfcrt in Laos, but for 195-268 kb (11-16 cM) in Thailand. Reduction in genetic variation was also less extreme in Laos than in Thailand. Most loci were monomorphic in a 12 kb region surrounding both genes on resistant chromosomes from Thailand, whereas in Laos, even loci immediately proximal to selective sites showed some variation on resistant chromosomes. Finally, linkage disequilibrium (LD) decayed more rapidly around resistant pfcrt and dhfr alleles from Laos than from Thailand. These results demonstrate that different realizations of the same selective sweeps may vary considerably in size and shape, in a manner broadly consistent with selection history. From a practical perspective, genomic regions containing resistance genes may be most effectively located by genome-wide association in populations exposed to strong drug selection. However, the lower levels of LD surrounding resistance alleles in populations under weak selection may simplify identification of functional mutations.
Journal Article > ResearchFull Text
Int J Health Geogr. 24 October 2016; Volume 15 (Issue 1); 37.; DOI:10.1186/s12942-016-0064-6
Grist EP, Fleqq JA, Humphreys G, Mas IS, Anderson TJC, et al.
Int J Health Geogr. 24 October 2016; Volume 15 (Issue 1); 37.; DOI:10.1186/s12942-016-0064-6
BACKGROUND
Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic 'smart surveillance' methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently.
METHODS
The approach uses the 'uncertainty' map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling.
RESULTS
The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion.
CONCLUSION
This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected areas.
Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic 'smart surveillance' methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently.
METHODS
The approach uses the 'uncertainty' map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling.
RESULTS
The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion.
CONCLUSION
This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected areas.
Journal Article > ResearchFull Text
Public Health Action. 4 November 2013; Volume 3 (Issue 1); S34-7.; DOI:10.5588/pha.13.0022
Naik B, Kumar AMV, Satyanarayana S, Suryakant MD, Swamy NMV, et al.
Public Health Action. 4 November 2013; Volume 3 (Issue 1); S34-7.; DOI:10.5588/pha.13.0022
SETTING
Seventeen peripheral health institutions (PHI) in Kolar district (population: 0.5 million), South India.
OBJECTIVE
To assess the feasibility and results of screening patients with tuberculosis (TB) for diabetes mellitus (DM) at peripheral level.
DESIGN
From January to September 2012, all TB patients were assessed for DM. Those with unknown DM status were screened for the disease (free of charge) by trained laboratory technicians at each PHI, using a glucometer supplied by the national programme on a capillary blood sample. Those with fasting blood glucose (FBG) ≥ 126 mg/dl (≥7 mM) were diagnosed as DM-positive.
RESULTS
Of 362 TB patients, 358 (99%) were assessed for DM and 62 (17.1%) had the diseases-53 (14.6%) had a previous history of DM and 9 (2.9%) were newly diagnosed. All new DM patients were enrolled into DM care. Higher DM prevalence was found among TB patients aged ≥40 years, smokers and those with smear-positive pulmonary TB. To detect a new case of DM, the number needed to screen (NNS) among TB patients was 40.
CONCLUSION
Screening of TB patients for DM was feasible and effective in a peripheral setting. The availability of trained laboratory technicians and free services at every PHI made the intervention feasible. The study has contributed towards a national policy decision in this regard.
Seventeen peripheral health institutions (PHI) in Kolar district (population: 0.5 million), South India.
OBJECTIVE
To assess the feasibility and results of screening patients with tuberculosis (TB) for diabetes mellitus (DM) at peripheral level.
DESIGN
From January to September 2012, all TB patients were assessed for DM. Those with unknown DM status were screened for the disease (free of charge) by trained laboratory technicians at each PHI, using a glucometer supplied by the national programme on a capillary blood sample. Those with fasting blood glucose (FBG) ≥ 126 mg/dl (≥7 mM) were diagnosed as DM-positive.
RESULTS
Of 362 TB patients, 358 (99%) were assessed for DM and 62 (17.1%) had the diseases-53 (14.6%) had a previous history of DM and 9 (2.9%) were newly diagnosed. All new DM patients were enrolled into DM care. Higher DM prevalence was found among TB patients aged ≥40 years, smokers and those with smear-positive pulmonary TB. To detect a new case of DM, the number needed to screen (NNS) among TB patients was 40.
CONCLUSION
Screening of TB patients for DM was feasible and effective in a peripheral setting. The availability of trained laboratory technicians and free services at every PHI made the intervention feasible. The study has contributed towards a national policy decision in this regard.