1 Introduction to the Karonga DSS Site (Karonga Continuous Registration System, CRS)

The Karonga programme began in 1978 with support from the British Leprosy Relief Association (LEPRA), as a population laboratory for evaluation of tools developed by the IMMLEP (Immunology of Leprosy) component of the WHO/TDR programme (the first skin and serological tests for M. leprae infection and an M. leprae antigen-based vaccine). It was designed initially as a large cohort study for risk factors of leprosy infection and disease, covering the entire district of Karonga (the population was selected because it had the highest burden of leprosy in that part of Africa). It assumed responsibility for tuberculosis diagnosis and treatment in the district in 1984, became the largest vaccine trial ever carried out in Africa in 1986 (comparing one versus two doses of BCG versus a combined BCG plus killed M. leprae vaccine, against both leprosy and tuberculosis) and began studies of HIV in 1987 (since which date an effort has been made to HIV test all leprosy and tuberculosis cases, and appropriate controls). The combined epidemiological and vaccine trial activities became known as the Karonga Prevention Study (KPS), by which name the project is still known. The trial codes were broken in 1995, revealing that BCG had provided appreciable protection against leprosy (50 % one dose; 75 % two doses) but none against tuberculosis.1 The trial results raised a variety of scientific questions, which, in combination with a unique sample archive and body of knowledge about the population, led to two Wellcome Trust supported programmes, first from 01/09/96 to 31/08/01 and the second (current) from 01/09/01 to 31/08/05. Throughout its history the programme has been linked closely to the London School of Hygiene & Tropical Medicine, for overall scientific direction, data management support, technical laboratory support, supplies and communication.

2 Physical Geography of the Karonga CRS

Karonga District is a rural area in northern Malawi, bordered by Lake Malawi on the east, the Songwe flood- plain and river on the north (the boundary with Tanzania) and the Central African plateau and Nyika escarpment on the west and south The terrain is varied, with a flat coastal plain along the lake, rising to hills and the plateau (c. 2600 m) to the west. The climate is appreciably wetter in the north than in the south of the District, which is reflected in differences in vegetation, agriculture and disease patterns (more leprosy, filariasis and schistosomiasis in the north). The people are of Bantu origin and include several language groups, predominantly Tumbuka in the south and Nkhonde in the northern part of the District. The population has more than doubled during the period of the project, from approximately 110,000 in 1980 and approaching 250,000 today. The district was without effective road access until 1981. There is now good road access both to the south (Mzuzu, the capital of Malawi’s northern region, is 2.5 hours away) and to the north (Mbeya in Tanzania, c. 3 hours). Lilongwe, Malawi’s capital and site of the nearest international airport, is 592 km and 6.5 hours away by road. The project’s headquarters are located near Chilumba, a port-village on the lake in the southern part of Karonga District. Most staff are based there, though some are based in Karonga Boma and in Kaporo, in the north. The area of the Karonga CRS is located in the south of the district near the project headquarters in Chilumba between latitudes 10.38° and 10.50°S and longitudes 34.08° and 34.27°E and covers an area of approx. 150 km2. The CRS area is unambiguously defined by the lake-shore in the east and the Nyika National Park boundary in the west, the north and the south delineation follow village boundaries. The CRS population is predominantly rural and the economy is based upon subsistence agriculture and fish from the lake. In these rural areas homesteads are scattered, however the area includes 2 peri-urban settlements, a truck stop and trading centre on the Trans-African Highway (M1) and the port-village of Chilumba where the settlement structure is dense. Approximately 5,000 population live in these peri-urban centres. 3 Karonga CRS data collection and processing

The baseline census for the Karonga CRS was started in 08/2002, and the demographic surveillance system was started in 10/2002. As of 11/2003 approx. 20,000 of the target population size of 35,000 are under demographic surveillance. Integrated into the census survey is a system of ‘census-tickets’ that is designed to facilitate the re-identification of known individuals seen in the census and also serves to update the KPS database. ‘Tickets’ and the accompanying set of booking registers are produced as an electronic report querying the database for all individuals whose last known residence is in the targeted village. The tickets of individuals who have died or left are used to record the year of death or the year of departure and the new residence. Basic socio-economic and demographic data and data needed to define the household identity are collected on one general household form per household. Demographic and basic health data are recorded on one census form per individual. Whenever available, health documents are used to record vaccination histories for all children under 5 and to supplement information on birth dates. The survival status and residence information is recorded for the parents of all individuals. The baseline census includes active case detection for TB (cough survey & on the spot sputum collection in suspicious cases) and a BCG-scar survey (identification and measurement of BCG scars) to link to previous work. Mapping: The GPS co-ordinates of all households are hand recorded by the booking team during the initial census and thereafter by the interviewers for every new household registered in the CRS. Village and cluster boundaries are tracked electronically by GPS using the village headman or a delegate as a guide. A selection of roads, tracks and footpaths as well as rivers and shoreline are also recorded in the field to be used as reference points for maps. The data recorded are transferred into ArcView for editing and hardcopy maps are produced that display all main landmarks and the cluster boundaries. The maps allow the field workers to allocate new households to the correct cluster and facilitate the retrieval of existing households during demographic surveillance. The Karonga CRS uses a key informant (KI) system for monthly vital registration and annual registration of migration. KIs are recruited in consultation with the village headman (whenever possible traditional village advisors ‘ndunas’ are selected) and grouped into reporting groups (approx. 10 KIs per reporting group). Each reporting group is trained in a formal and standardised training session after the baseline survey in the area has been completed. KIs are responsible for a geographically defined cluster comprising on average 35 households (190 individuals) and are issued with a household register that is produced from the CRS database. There is a monthly reporting session for each reporting group where the KIs meet with the CRS supervisor to report all vital events. Births are followed up by the CRS supervisor within 2 days of the report when he fills a special birth registration form. Deaths are followed up by a medical assistant at an appropriate time allowing for a 2 week mourning period. VAs are done for all deaths. The monthly follow up of all vital events triggers a complete observation of the respective household and any migrations found in the household are registered opportunistically at that time. Movements within the CRS are concluded without delay by filling the departure form at the departure household and an arrival form at the arrival household which is visited in all cases. After 11 months, a special training session is organised to prepare the reporting group for the complete registration of all migrations that have occurred since the baseline survey or the previous annual update session (AUS). In the month before the AUS, the KIs are requested to visit every household in their cluster and record any changes systematically in their household register. At the AUS, the CRS supervisor takes the reports of new households and movements; households with vital events or in- migrations are visited and the events are registered by filling the appropriate forms. Households with only departures are not visited but dealt with at the AUS by using the KIs to fill the departure forms. All forms are returned to the data office where they are checked and processed by 3 trained coders and double entered by 2 data entry clerks. The design of the CRS data management system has proven a significant challenge since it was desired to link tightly to the project’s existing database. The KPS database originates from 2 whole population surveys of the district that were conducted in the 1980s and has been continuously maintained for 24 years. It stores the identifiers of 260,000 individuals (approximately 60% of the population alive in the district today) whose residence and survival status has been updated opportunistically in the context of various studies conducted since the first surveys. Each individual has had on average 2.3 study contacts since the start of the project in 1979 and the project staff has developed exceptional skills and dedication to correctly identify individuals by matching information collected in the field with the details held on the database. The CRS data management system has an Access front-end and links to its private Access database and to the pre-existing non-relational FoxPro database. A series of batch checks is run for each reporting group before their monthly reporting session and all errors or inconsistencies that cannot be corrected by the coders are returned to the field staff.

4 Karonga CRS Basic Output

The actual demographic surveillance in the first reporting group started in 10/2002 and demographic indicators of the Karonga CRS will be available once the baseline census is completed and all reporting groups have accomplished 12 months surveillance. Besides the basic demographic indicators, the Karonga CRS will provide data on cause specific mortality (obtained by VA) for all age-groups and migration data for individuals on the level of the social group and for whole households on the level of the geographical cluster. Priority Research Areas The current multidisciplinary research programme at KPS concentrates on three broad project areas: immunological studies comparing T cell memory and responses to BCG between infants and adults, and between Malawi and the UK; expanded epidemiological studies of tuberculosis; and the initiation of a demographic surveillance system with emphasis on HIV-related studies. The demographic surveillance system at KPS was designed to measure the impact of the HIV epidemic in Karonga District. The Karonga CRS was tailored to maximise the overlap with a population based HIV cohort study (Family Health Study) that was conducted during the previous research programme. In preparation for operational research into the modes of delivery of PMTCT the CRS area was also designed to match the catchment area of 2 ANC clinics in the south of the district. We are hoping to contribute to the assessment of the practicalities and the impact of large-scale introduction of HAART in a rural setting. As in the previous programmes the project continues to be interested in vaccine related research and data on vaccination histories are routinely collected from all children under 5 seen in the census.

5 Capacity for Conducting Clinical Trials

Although clinical trials are not part of our current work, KPS has significant experience in conducting a TB vaccine trial in collaboration with a 2nd study site in Zambia and the National TB Control Programme, Malawi. The TB vaccine trial became the largest vaccine trial ever carried out in Africa in 1986 (comparing one versus two doses of BCG versus a combined BCG plus killed M. leprae vaccine, against both leprosy and tuberculosis, see publication list). Potential future clinical trials at KPS would have to be designed considering the very basic standard of the district health system and may require considerable investment into clinical facilities.

6 Description of Clinical Facilities

The government clinical facilities in Karonga District are basic even by Malawian standards and KPS does not have any clinical facility of its own. However, the project used to have staff based at all hospitals and health centres in the district during the leprosy and TB vaccine trials. In the current studies staff are maintained in the district hospital and 3 other rural health facilities including Chilumba Rural Hospital (CRH) close to the project headquarters. There are currently 4 clinicians working at KPS (see staff list), 2 of which are carrying out regular clinical responsibilities in the infant study and in TB case ascertainment. The project currently employs the only radiographer and x-ray technician in the district who is based at the district hospital and splits his time between study work and routine clinical services. 12 project paramedical staff dedicate part of their time to see referrals for skin conditions and leprosy suspects. From the census camp, KPS runs a weekly skin / TB case-finding clinic for self-referrals and patients met in the baseline census. KPS maintains close co-operation with the National TB Control Programme.

7 Laboratory Facilities at KPS

All specimens (~30 per day) are brought to the central laboratory reception area for electronic registration. This involves computer-entry of identification and test details from the field specimen form, computer assignment of lab numbers and then separation for their destination laboratory. The free-standing Category 3 laboratory suite was purpose-built with Wellcome Trust support, commissioned in 2000 and operates to high safety standards comparable with the UK. It is used for mycobacteriology and for other high-risk samples. It is air conditioned, has two Class 1 safety cabinets, one centrifuge, 3 incubators, 5 refrigerators, 1 -70oC freezer, fluorescence microscope, sink (for slide staining) and a hand basin. The majority of the workload consists of smear (Auramine screen confirmed by ZN) and culture (Lowenstein Jensen) of M. tuberculosis (mainly sputa, 3000 per annum), fungal microscopy (KOH method), malaria films (Field’s stain, primarily for staff) and slit skin smears for leprosy (ZN). There is an air conditioned tissue culture room within the Category 3 laboratory with one Class 2 safety cabinet and CO2 incubator, for whole blood assays of high risk samples (HIV positives, tuberculosis cases and contacts). There is also a sterilising room with two bench-top autoclaves and wash-up facilities. All Category 3 waste is autoclaved and then burnt. A separate Category 2 laboratory building accommodates laboratories, offices (laboratory manager’s and immunologist’s) and the computer server room. The immunology laboratory is used for serum separation, serology (HIV by Edgware particle agglutination and Vironostika Uniform II for blood, GACELISA for saliva; syphilis by RPR and TPPA; HSV2 by Kalon IgG ELISA) and DNA extraction (Nucleon). It contains an ELISA reader, 2 centrifuges, 2 freezers, networked computer and bench top autoclave. An attached tissue culture suite with Class 2 cabinet and CO2 incubator is used for whole blood and T cell assays of low risk specimens. There is a air-conditioned flow cytometry room containing a 4-colour flow cytometer (FACSCalibur) for T cell immunology studies and CD4 counts. A dedicated parasitology laboratory is used for stool (Kato-Katz and Parasept) and urine (formalised sedimentation) samples. The project has –20 and –70 freezer facilities.

8 List of Scientists

8.1 Dedicated to DSS

PI: Basia Zaba, LSHTM, UK Karonga CRS field leader: Andreas Jahn, clinical epidemiologist, KPS Malawi Data-management: Keith Branson, Jacky Saul, programmers, LSHTM, UK Project Statistician: Sian Floyd, LSHTM, UK Field Staff: 8 trained full time interviewers (baseline census, mapping, continuous demographic surveillance) 1 medical assistant to conduct all verbal autopsies Office Staff: 2,5 trained coders, 2 trained data-entry clerks 8.2 Other KPS Projects

PI’s: Prof Paul Fine, LSHTM , Prof Hazel Dockrell, LSHTM, UK Field director: Amelia Crampin, clinical epidemiologist, KPS, Malawi Scientific Staff: Anne Ben-Smith, immunologist, KPS, Malawi Frank Mwaungulu, assistant field director, medical officer, KPS, Malawi Hazzie Mvula, paediatrician, clinical officer, KPS, Malawi Other Malawi based staff: 2 senior technical support staff, 3 administrative staff, 15 data office staff, 20 paramedic, 5 laboratory technicians, 32 technical & ancillary staff

9 Catalogue of completed and ongoing projects

9.1 Completed Research Projects

Pre-Wellcome Trust Period: see introduction and publication list FIRST WELLCOME TRUST PROGRAMME (01 Sept 1996 – 31 Aug 2001): This programme centred around four project areas: genetics of leprosy and tuberculosis; immune responses to BCG vaccine in Malawi (with comparative studies in the UK, funded by WHO and LEPRA); tuberculosis epidemiology; and HIV epidemiology

9.2 Ongoing Research Projects

SECOND WELLCOME TRUST PROGRAMME (01 Sept 2001– 31 Aug 2005): The second (current) programme concentrates upon three broad project areas: the initiation of a demographic surveillance system with emphasis on HIV-related studies, immunological studies comparing T cell memory and responses to BCG between infants and adults, and between Malawi and the UK; and expanded epidemiological studies of tuberculosis.

9.3 Projects that have directly influenced national health policy

The ability of co-trimoxazole to reduce mortality in HIV-positive tuberculosis has been an important issue in Africa since the initial report from Cote d’Ivoire in 1999. Because of that report, controlled trials of the intervention in South Africa and Malawi were stopped as unethical, despite a lingering concern that the intervention might not be as effective in Eastern and Southern Africa as in West Africa, because of differences in opportunistic pathogens and drug sensitivity patterns. An opportunity to test the intervention arose in Karonga because of the availability of appropriate historical controls with known HIV status. The proposal was supported by DfID and the work carried out in collaboration with the National Tuberculosis Control Programme. A parallel study was carried out at the same time in Thyolo District, in southern Malawi, though without historical HIV data. During the year 2000, all consenting HIV-positive registered TB patients in Karonga were offered co- trimoxazole prophylaxis. Co-trimoxazole was started as soon as the HIV-positive test result was known, at a dose of 960mg daily. It was administered with the anti-tuberculosis drugs under direct supervision for those hospitalised in the wards (during the intensive phase of treatment) and was given unsupervised to those taking continuation phase treatment in the community. The drug was given for the duration of one year to all study patients. For those on continuation phase, monthly supplies of the drugs were given together with their monthly supplies of TB drugs. Patients were followed up for 18 months. Case fatality rates were unchanged between the 2 years in HIV-negative patients (suggesting the historical controls were appropriate), but fell in HIV-positive patients from 43% to 24%. The improved survival became apparent after the first two months and was maintained beyond the end of treatment. It was most marked in patients with smear positive TB and others with confirmed TB diagnoses. Findings in Thyolo district were consistent with this. These results were presented to the National Tuberculosis Control Programme in 2002, leading to a change in national policy, recommending voluntary counselling and testing, followed by co-trimoxazole prophylaxis for all HIV positive tuberculosis patients. This policy is now being introduced in a phased manner throughout the country, with Karonga among the first districts to implement it.

10 Publications

I JOURNAL ARTICLES 1. Jones RL, Pönnighaus JM. The transport of histopathological specimens by airmail. Leprosy Review 1982; 53: 67-68. 2. Sliney I, Pönnighaus JM, Fine PEM. Barriers to progress and the Lepra Evaluation Project (LEP). Malawi Epidemiological Quarterly 1984; 1: 28-32. 3. Pönnighaus JM, Fine PEM. Sensitization studies with potential leprosy vaccine preparations in Northern Malawi. International Journal of Leprosy 1986; 54: 25-37. 4. Fine PEM, Job CK, McDougall AC, Meyers WM, Pönnighaus JM. Comparability among histopathologists in the diagnosis and classification of lesions suspected of leprosy in Malawi. International Journal of Leprosy 1986; 54: 614-625. 5. Fine PEM, Pönnighaus JM, Maine N, Clarkson JA, Bliss L. Protective efficacy of BCG against leprosy in Northern Malawi. Lancet 1986; ii: 499-502. 6. Pönnighaus JM, Fine PEM. The Karonga Prevention Trial - which BCG? Leprosy Review 1986; 57 (Suppl): 285-292. 7. Fine PEM, Pönnighaus JM, Maine NP. The relationship between delayed type hypersensitivity and protective immunity induced by mycobacterial vaccines in man. Leprosy Review 1986; 57 (Suppl): 275- 283. 8. Boerrigter G, Pönnighaus JM. Ten years' leprosy control work in Malawi (central Africa) - I. - Methods and outcome after treatment. Leprosy Review 1986; 57 199-219. 9. Pönnighaus JM, Boerrigter G. Ten years' leprosy control work in Malawi (central Africa) - II. - Patterns of endemicity since 1973. Leprosy Review 1986; 57 221-236. 10. Boerrigter G, Pönnighaus JM. Preliminary evaluation of the effect of WHO-MDT on disabilities in leprosy patients in Malawi (Central Africa). Leprosy Review 1986; 57 Suppl 3: 101-105. 11. McDougall AC, Pönnighaus JM, Fine PEM. Histopathological examination of skin biopsies from an epidemiological study of leprosy in northern Malawi. International Journal of Leprosy 1987; 55: 88-98. 12. Pönnighaus JM, Fine PEM, Bliss L. Certainty levels in the diagnosis of leprosy. International Journal of Leprosy 1987; 55: 454-462. 13. Pönnighaus JM, Fine PEM, Bliss L, Sliney IJ, Bradley DJ, Rees RJW. The Lepra Evaluation Project (LEP), an epidemiological study of leprosy in Northern Malawi. I. Methods. Leprosy_Review 1987; 58: 359-375. 14. Pönnighaus JM, Fine PEM, Maine N, Bliss L, Kalambo M, Pönnighaus I. The Lepra Evaluation Project (LEP), an epidemiological study of leprosy in Northern Malawi. II. Prevalence rates. Leprosy_Review 1988; 59: 97-112. 15. Burgess PJ, Fine PEM, Pönnighaus JM, Draper CC. Serological tests in leprosy. The sensitivity, specificity and predictive value of ELISA tests based on phenolic glycolipid antigens, and the implications for their use in epidemiological studies. Epidemiology and Infection 1988; 101: 159-171. 16. Boerrigter G, Pönnighaus JM, Fine PEM. Preliminary appraisal of a WHO-recommended multiple drug regimen in paucibacillary leprosy patients in Malawi. International Journal of Leprosy 1988; 56: 408-417. 17. Fine PEM, Pönnighaus JM, Burgess P, Clarkson JA, Draper CC. Seroepidemiological studies of leprosy in northern Malawi based on an enzyme-linked immunosorbent assay using synthetic glycoconjugate antigen. International Journal of Leprosy 1988; 56: 243-254. 18. Pönnighaus JM, Fine PEM. Sensitivity and specificity of the diagnosis, and the search for risk factors for leprosy. Transactions of the Royal Society of Tropical Medicine and Hygiene 1988; 82: 803-809. 19. Fine PEM, Pönnighaus JM. Background, design and prospects of the Karonga Prevention Trial, a leprosy vaccine trial in Northern Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene 1988; 82: 810-817. 20. Fine PEM, Pönnighaus JM, Maine N. The distribution and implications of BCG scars in Northern Malawi. Bulletin of the World Health Organization 1989; 67 (1):35-42. 21. Fine PEM, Gruer PJK, Maine N, Pönnighaus JM, Rees RJW, Stanford JL. Failure of Mycobacterium leprae soluble antigens to suppress delayed-type hypersensitivity reaction to tuberculin. Clinical and Experimental Immunology 1989; 77: 226-229. 22. Pönnighaus JM, Fine PEM. A comparison of sensory loss tests and histopathology in the diagnosis of leprosy. Leprosy Review 1989; 60: 20-27. 23. Pönnighaus JM, Fine PEM, Gruer PJK, Maine N. The anatomical distribution of single leprosy lesions in an African population, and its implications for the pathogenesis of leprosy. Leprosy Review 1990; 61: 242-250. 24. Pönnighaus Ita M, Boerrigter G, Fine PEM, Ponnighaus JM, Russell J. Disabilities in leprosy patients ascertained in a total population survey in Karonga District, Northern Malawi. Leprosy Review 1990; 61: 366-374. 25. Shaw M, Turner AC, Blackwell JM, Fine PEM, Pönnighaus JM. Setting up HIV serology for the Karonga leprosy vaccine trial in Malawi. Leprosy Review 1991; 62: 87-104. 26. Boerrigter G, Pönnighaus JM, Fine PEM, Wilson RJ. Four year follow-up results of a WHO- recommended multiple-drug regimen in paucibacillary leprosy patients in Malawi. International Journal of Leprosy 1991; 59: 255-261. 27. Pönnighaus JM, Mwanjasi LJ, Fine PEM, Shaw M, Turner AC, Oxborrow SM, Lucas SB, Jenkins PA, Sterne JAC, Bliss L. Is HIV infection a risk factor for leprosy? International Journal of Leprosy 1991; 59: 221-228. 28. Pönnighaus JM, Fine PEM, Sterne JAC, Wilson RJ, Msosa E, Gruer PJK, Jenkins PA, Lucas SB, Liomba G, Bliss L. Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi. Lancet 1992; 339: 636-639. 29. Pönnighaus JM, Fine PEM, Sterne JAC, Lucas SB, McDougall AC. Long-term active surveillance of leprosy suspects - what are the likely returns? Leprosy Review 1993; 64: 25-36. 30. Sterne JAC, Turner AC, Connell JA, Parry JV, Fine PEM, Pönnighaus JM, Nyasulu S, Mkandwire K. Human immunodeficiency virus: GACPAT and GACELISA as diagnostic tests for antibodies in urine Transactions of the Royal Society of Tropical Medicine and Hygiene 1993; 87: 181-183. 31. Fine PEM, Job CK, Lucas SB, Meyers WM, Pönnighaus JM, Sterne JAC. Extent, origin and implications of observer variation in the histopathological diagnosis of suspected leprosy. International Journal of Leprosy 1993; 61: 270-282 32. Pharoah PDP, Pönnighaus JM, Lucas SB. Two cases of cutaneous leishmaniasis in Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene 1993; 87: 668-670. 33. Pönnighaus JM, Fine PEM, Bliss L, Gruer PJK, Kapira-Mwamondwe B, Msosa E, Rees RJW, Clayton D, Pike MC, Sterne JAC, Oxborrow SM. The Karonga Prevention Trial: a leprosy and tuberculosis vaccine trial in Northern Malawi. I. Methods of the vaccination phase. Leprosy Review 1993; 64: 338- 356. 34. Pönnighaus JM, Fine PEM, Sterne JAC, Bliss L, Wilson RJ, Malema SS, Kileta S, Incidence rates of leprosy in Karonga District, Northern Malawi: patterns by age, sex, BCG status and classification. International Journal of Leprosy 1994; 62: 10-23. 35. Pönnighaus JM, Gooskens V, Clayton Y, Mkandawire P, Sterne J. Treatment of superficial mycoses in the Tropics. Results of a double-blind trial in Karonga District, Malawi. Mycoses 1994; 37: 101-104. 36. Gooskens V, Pönnighaus JM, Clayton Y, Mkandwire P, Sterne JAC. Treatment of superficial mycoses in the tropics - Whitfield’s ointment versus clotrimazole. International Journal of Dermatology 1994; 33: 738-42. 37. Pönnighaus JM, Fine PEM, Sterne JAC, Malema SS, Bliss L, Wilson RJ (1994) Extended schooling and good housing conditions are associated with reduced risk of leprosy in rural Malawi. International Journal of Leprosy 1994; 62: 345-352. 38. Fine PEM, Sterne JAC, Pönnighaus JM, Rees RJW, Delayed-type hypersensitivity, mycobacterial vaccines and protective immunity. Lancet 1994; 344: 1245-49. 39. Pönnighaus JM, Boerrigter G. Are 18 doses of WHO/MDT sufficient for multibacillary leprosy: results of a trial in Malawi, International Journal of Leprosy 1995; 63: 1-7. 40. Glynn JR, Jenkins PA, Fine PEM, Pönnighaus JM, Sterne JAC, Mkandwire PK, Nyasulu S, Bliss L, Warndorff DK. Patterns of initial and acquired antituberculosis drug resistance in Karonga District, Malawi. Lancet 1995; 345: 907-910. 41. Pönnighaus JM, Sterne JAC. Epidemiological aspects of relapses in leprosy. Indian Journal of Leprosy 1995; 67: 35-44. 42. Sterne JAC, Turner AC, Fine PEM, Parry JV, Lucas SB, Pönnighaus JM, Mkandwire PK, Nyasulu S, Warndorff DK. Testing for antibody to human immunodeficiency virus type 1 in a population in which mycobacterial diseases are endemic, Journal of Infectious Diseases 1995; 172: 543-6. 43. Sterne JAC, Pönnighaus JM, Fine PEM, Malema M. Geographic determinants of leprosy in Karonga District, Northern Malawi, International Journal of Epidemiology 1995; 24: 1211-22. 44. Pönnighaus JM, Warndorff D and Port G. Microsporum nanum - a report from Malawi. Mycoses 1995; 38: 149-150. 45. Sterne JAC, Fine PEM, Pönnighaus JM, Sibanda F, Munthali M. Does bacille Calmette-Guérin scar size have implications for protection against tuberculosis or leprosy. Tubercle and Lung Disease 1996; 77: 117-123. 46. Pönnighaus JM, Clayton Y, Warndorff D. The spectrum of dermatophytes in northern Malawi (Africa), Mycoses 1996; 39: 293-297. 47. Pönnighaus JM. Diagnosis and Management of single lesions in leprosy. Leprosy Review 1996; 67: 89-94. 48. Pönnighaus JM, Fine PEM, Saul J. The epidemiology of pityriasis versicolor in Malawi, Africa. Mycoses 1996; 39, 467-470. 49. Karonga Prevention Trial Group. Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi Lancet, 1996; 348: 17-24. 50. Warndorff DK, Glynn JR, Fine PEM, Jamil S de Wit, Madeleine YL, Munthali MM, Stoker NG, and Klatser PR. Polymerase chain reaction of nasal swabs from tuberculosis patients and their contacts, International Journal of Leprosy 1996; 64: 404-408. 51. Warndorff DK. Tuberculosis prevention: where do we go from here? Africa Health November 1996. 52. Fine PEM, Sterne JAC, Pönnighaus JM, Bliss L, Saul J, Chihana A, Munthali M, Warndorff DK. Household and dwelling contact as risk factors for leprosy in northern Malawi, American Journal of Epidemiology 1997; 146: 91-102 53. Glynn JR, Warndorff DK, Fine PEM, Msiska GK, Munthali MM, Pönnighaus JM. The impact of HIV on morbidity and mortality from tuberculosis in sub-Saharan Africa : a study in rural Malawi and review of the literature. Health Transition Review 1997; 7: 75-87 54. Pönnighaus JM, Lienhardt C, Lucas S, Fine PEM, Sterne JAC. Comparison of bacillary indexes in slit- skin smears, skin and nerve biopsies; a study from Malawi. International Journal of Leprosy 1997; 65: 211-216. 55. Fine PEM, Warndorff DK. Leprosy by the year 2000 - what is being eliminated? Leprosy Review 1997; 68: 201-202. 56. Glynn JR, Warndorff DK, Fine PEM, Munthali MM, Sichone W, Pönnighaus JM. Measurement and determinants of tuberculosis outcome in Karonga District, Malawi. Bulletin of the World Health Organisation 1998; 76: 295-305. 57. Sterne JAC, Fine PEM, Pönnighaus JM, Rees RJW, Chavula D. Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus. International Journal of Epidemiology 1998; 27: 713-721. 58. Fine PEM, Bruce J, Pönnighaus JM, Nkhosa P, Harawa A., Vynnycky E. Tuberculin sensitivity: conversions and reversions in a rural African population. International Journal of Tuberculosis and Lung Disease 1999; 3: 962-975. 59. Glynn JR, Warndorff DK, Malema SS, Mwinuka V, Ponnighaus JM, Turner AC, Crampin A, Fine PEM. Risk factors for tuberculosis (TB) in a rural African population cohort with known HIV status. Tuberculosis Surveillance Research Unit Progress Report 1999 – Vol 2: 79-85. 60. Mendum TA, Chilima BZ, Hirsch PR. The PCR amplification of non-tuberculous mycobacterial 16S rRNA sequences from soil. FEMS Microbiology Letters 2000; 185: 189-192. 61. Warndorff DK, Yates M, Ngwira B, Chaguluka S, Jenkins PA, Drobniewski F, Pönnighaus JM, Glynn JR, Fine PEM. Trends in antituberculosis drug resistance in Karonga District Malawi, 1986-1998. International Journal of Tuberculosis and Lung Disease 2000; 4: 752-757. 62. Floyd S, Pönnighaus JM, Bliss L, Warndorff DK, Kasunga A, Mogha P, Fine PEM. BCG scars in northern Malawi: sensitivity and repeatability of scar reading, and factors affecting scar size. International Journal of Tuberculosis and Lung Disease 2000; 4: 1133-1142. 63. Glynn JR, Warndorff DK, Malema SS, Mwinuka V, Pönnighaus JM, Crampin AC, Fine PEM. Tuberculosis: associations with HIV and socioeconomic status in rural Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000; 94: 500-503. 64. Dockrell HM, Black GF, Weir RE, Fine PEM. Whole blood assays for interferon-?: practicalities and potential for use as diagnostic tests in the field. Leprosy Review Proceedings of “Leprosy Research at the new millennium” workshop, Paris 26-28 June 2000. 71: S60-S62. 65. Fine PEM, Floyd S, Stanford JL, Nkhosa P, Kasunga A, Chaguluka S, Warndorff DK, Jenkins PA, Yates M, Pönnighaus JM. Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy. Epidemiology and Infection 2001; 126: 379-387. 66. Crampin AC, Mwinuka V, Malema SS, Glynn JR, Fine PEM. Field based random sampling without a sampling frame: control selection for a case control study in rural Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 2001; 95: 481-483. 67. Black GF, Fine PEM, Warndorff DK, Floyd S, Weir RE, Blackwell JM, Bliss L, Sichali L, Mwaungulu L, Chaguluka S, Jarman E, Ngwira B, Dockrell, HM. Relationship between IFN-? and skin test responsiveness to Mycobacterium tuberculosis PPD in healthy, non-BCG-vaccinated young adults in northern Malawi. International Journal of Tuberculosis and Lung Disease 2001; 5: 664-672. 68. Black GF, Dockrell HM, Crampin AC, Floyd S, Weir RE, Bliss L, Sichali L, Mwaungulu L, Kanyongoloka H, Ngwira B, Warndorff DK, Fine PEM. Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi. Journal of Infectious Diseases 2001; 184: 322-329. 69. Glynn JR, Pönnighaus JM, Crampin AC, Sibande F, Sichali L, Nkhosa P, Broadbent P, Fine PEM. The development of the HIV epidemic in Karonga District, Malawi. AIDS 2001; 15: 2025-2029. 70. Crampin AC, Damisoni H. HIV/AIDS testing and counselling. Leprosy Review 2001; 72: 345-351. 71. Pönnighaus JM, Nkhosa P, Baum H-P. Kutane Manifestation der Zystizerkose (Cutaneous manifestation of cysticercosis). Hautarzt 2001; 52: 1098-1100. 72. Crampin AC, Floyd S, Mwaungulu F, Black GF, Ndhlovu R, Mwaiyeghele E, Glynn JR, Warndorff DK, Fine PEM. Comparison of two versus three smears in identifying culture positive tuberculosis patients in a rural African setting with high HIV prevalence. International Journal of Tuberculosis and Lung Disease 2001; 5: 994-999. 73. Randall AE, Perez MA, Floyd S, Black GF, Crampin AC, Ngwira B, Pistoni WN, Mulawa D, Sichali L, Mwaungulu L, Bickle Q, Fine PEM. Patterns of helminth infection and relationship to BCG vaccination in Karonga District, northern Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene 2002; 96: 29-33. 74. Black GF, Weir RE, Floyd S, Bliss L, Warndorff DK, Crampin AC, Ngwira B, Sichali L, Nazareth B, Blackwell JM, Branson K, Chaguluka SD, Donovan L, Jarman E, King E, Fine PEM, Dockrell HM. BCG- induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet 2002; 359: 1393-1401. 75. Crampin AC, Mwaungulu FD, Floyd S, Black GF, Ndhlovu R, Mwaiyeghele E, Glynn JR, Fine PEM. The value of two versus three smears in identifying culture positive tuberculosis patients in Karonga district. Malawi Medical Journal 2002; 13: 9-11. 76. Mwaungulu FD, Crampin AC, Chaguluka S, Mwafulirwa DT, Mwaungulu NJ, Glynn JR, Yates M, Drobniewski F, Fine PEM. Antituberculosis drug resistance in Karonga District: Pattern and trend 1986- 2001. Malawi Medical Journal 2002; 13: 3-6. 77. Ngwira BMM, Chaguluka S, Warndorff DK, Branson K, Lucas SB, Fine PEM. Development of a scoring system for the diagnosis of tuberculous lymphadenitis. Malawi Medical Journal 2002; 13: 14-16. 78. Brandt L, Cunha JF, Olsen AW, Chilima B, Hirsch P, Appelberg R, Andersen P. Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis. Infection and Immunity 2002; 70: 672-678. 79. Ngwira BMM, Jabu CH, Kanyongoloka H, Mponda M, Crampin AC, Branson K, Alexander NDE, Fine PEM. Lymphatic filariasis in Karonga District – northern Malawi: a prevalence survey. Annals of Tropical Medicine & Parasitology 2002; 96: 137-144. 80. Crampin AC, Floyd S, Glynn JR, Sibande F, Mulawa D, Nyondo A, Broadbent P, Bliss L, Ngwira B, Fine PEM. Long term follow-up of HIV positive and negative individuals in rural Malawi. AIDS 2002; 16: 1545-1550. 81. Floyd S, Pönnighaus JM, Bliss L, Nkhosa P, Sichali L, Msiska G, Fine PEM. Kinetics of delayed-type hypersensitivity to tuberculin induced by BCG vaccination in northern Malawi. Journal of Infectious Diseases 2002; 186: 807-814. 82. Mwinga A, Nunn A, Ngwira B, Chifumbe C, Warndorff DK, Fine PEM, Darbyshire J, Zumla A. Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial. Lancet 2002; 360: 1050-1055. 83. McCormack GP, Glynn JR, Crampin AC, Sibande F, Mulawa D, Bliss L, Broadbent P, Abarca K, Pönnighaus JM, Fine PEM, Clewley JP. Early evolution of the Human Immunodeficiency Virus type 1 subtype C epidemic in rural Malawi. Journal of Virology 2002; 76: 12890-12899. 84. Fitness J, Tosh K, Hill AVS. Genetics of susceptibility to leprosy. Genes and Immunity 2002; 3: 441- 453. 85. Crampin AC, Floyd S, Glynn JR, Madise N, Nyondo A, Khondowe MM, Njoka CL, Kanyongoloka H, Ngwira B, Zaba B, Fine PEM. The long-term impact of HIV and orphanhood on the mortality and physical well-being of children in rural Malawi. AIDS 2003; 17: 389-397. 86. Wallace C, Clayton D, Fine PEM. Estimating the relative recurrence risk ratio for leprosy in Karonga district, Malawi. Leprosy Review 2003; 74: 133-140. 87. McCormack GP, Glynn JR, Crampin AC, Sibande F, Mulawa D, Fine PEM, Clewley JP. Highly divergent HIV-1 group M sequences evident in Karonga District, Malawi in the early 1980’s. AIDS Research and Human Retroviruses 2003; 19: 441-445. 88. Black GF, Weir RE, Chaguluka SD, Warndorff D, Crampin AC, Mwaungulu L, Sichali L, Floyd S, Bliss L, Jarman E, Donovan L, Andersen P, Britton W, Hewinson G, Huygen K, Paulsen J, Singh M, Prestidge R, Fine PEM, Dockrell HM. Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-mycobacterium bovis BCG-vaccinated Malawian young adults. Clinical and Diagnostic Laboratory Immunology 2003; 10: 602-611. 89. Crampin AC, Glynn JR, Ngwira BMM, Mwaungulu FD, Pönnighaus JM, Warndorff DK, Fine PEM. Trends and measurement of HIV prevalence in northern Malawi, 1988-2001. AIDS 2003; 17: 1817- 1825. 90. Wallace C, Clayton D. Estimating the relative recurrence risk ratio using a global cross ratio model. Genetic Epidemiology (In press). 91. Crampin AC, Glynn JR, Floyd S, Malema SS, Mwinuka VK, Ngwira BMM, Mwaungulu FD, Warndorff DK, Fine PEM. Tuberculosis and gender: exploring the patterns in a case control study in Malawi. International Journal of Tuberculosis and Lung Disease (In press). 92. Weir RE, Fine PEM, Nazareth B, Floyd S, Black GF, King E, Stanley C, Bliss L, Branson K, Dockrell HM. Interferon-? and skin test responses of schoolchildren in southeast England to purified protein derivaties from Mycobacterium tuberculosis and other species of mycobacteria. Clinical and Experimental Immunology (In press). 93. Mwaungulu FBD, Floyd S, Crampin AC, Kasimba S, Malema S, Kanyongoloka H, Harries AD, Glynn JR, Fine PEM. Cotrimoxazole prophylaxis reduces mortality in HIV-positive tuberculosis patients in Karonga District, Malawi. Bulletin of WHO (In press). 94. Zaba B, Marston M, Floyd S. The effect of HIV on child mortality trends in sub-Saharan Africa UN Population Bulletin (In press). 95. Weir RE, Black GF, Dockrell HM, Floyd S, Fine PEM, Chaguluka SD, Stenson S, King E, Nazareth B, Warndorff DK, Ngwira B, Crampin AC, Mwaungulu L, Sichali L, Jarman E, Donovan L, Blackwell JM. Mycobacterial PPDs stimulate innate immunity: Malawians show enhanced TNFa, IL-1ß and IL-10 responses compared to UK adolescents (Submitted). 96. Fitness J, Floyd S, Warndorff DK, Sichali L, Mwaungulu L, Crampin AC, Fine PEM, Hill AVS. Large scale candidate gene study of leprosy susceptibility in Karonga District, northern Malawi (Submitted). 97. Fitness J, Floyd S, Warndorff DK, Sichali L, Malema S, Crampin AC, Fine PEM, Hill AVS. Large scale candidate gene study of tuberculosis susceptibility in Karonga District, northern Malawi (Submitted). 98. Wallace C, Fitness J, Hennig B, Sichali L, Mwaungulu L, Pönnighaus JM, Warndorff DK, Clayton D, Fine PEM, Hill AVS. Linkage analysis of susceptibility to leprosy type (Submitted). 99. Zaba B, Marston M, Nakiyingi J, Whitworth J, Ruberantwari A, Urassa M, Issingo R, Mwaluko G, Crampin AC, Floyd S, Nyondo A. HIV and mortality of mothers and children: evidence from cohort studies in Uganda, Tanzania and Malawi (Submitted). 100. Floyd S, Crampin AC, Glynn JR, Madise N, Mwenebabu M, Mlenga L, Mnkhondia S, Ngwira B, Zaba B, Fine PEM. The impact of HIV on household structure in rural Malawi (Submitted). 101. Kläger SL, Black GF, Floyd S, Perez M, Bliss L, Crampin AC, Ngwira B, Mwaungulu L, Chaguluka SD, Sichali L, Bickle Q, Fine PEM, Dockrell HM. IL-5 and IFN-? responses to Mycobacterium tuberculosis PPD in relation to multiple helminth infections (Submitted). 102. Black GF, Weir RE, Floyd S, Chaguluka SD, Jarman E, Donovan L, Mwanyimboa A, Sichali L, Crampin AC, Fine PEM, Dockrell HM. IL-5 responses following BCG vaccination of young adults in Malawi: T cell responses to Mycobacterium tuberculosis PPD do not show a Th1/Th2 dichotomy (Submitted). 103. Glynn JR, Crampin AC, Ngwira BMM, Mwaungulu FD, Mwafulirwa DT, Floyd S, Ponnighaus JM, Warndorff DK, Fine PEM. Trends in tuberculosis and the influence of HIV infection in northern Malawi, 1988-2001 (Submitted). 104. Fitness J, Siddiqui MR, Wallace C, Aucan C, Warndorff DK, Sichali L, Mwaungulu L, Hill AVS, Fine PEM. No evidence for a major locus of leprosy susceptibility on chromosome 10p13 in Karonga District, Malawi (Submitted). 105. Johnson JL, Nunn AJ, Fourie PB, Ormerod P, Mugerwa RD, Chintu C, Ngwira B, Onyebujoh P, Zumla A. Effect of Mycobacterium vaccae immunotherapy on radiographic healing in tuberculosis (Submitted). II LETTERS 1. Pönnighaus JM, Oxborrow SM. Construction projects and spread of HIV. Lancet 1990; ii: 1198. 2. Pönnighaus JM, Oxborrow SM. Counselling HIV positive leprosy patients. Leprosy Review 1991; 62: 105. 3. Pönnighaus JM, Fine PEM, Moreno C. Hypersensitivity to dextran in BCG vaccine. Lancet 1991; 337: 1039 . 4. Pönnighaus JM. HIV-1 Infection and Leprosy, International Journal of Leprosy, 1994; 62: 611-612. (Letter reply). 5. Munthali MM, Warndorff DK, Koka CW, Glynn JR, Salaniponi FLM. Thiacetazone reactions in Northern Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene 1994; 89: 238. 6. Lucas SB, Fine PEM, Sterne JAC, Pönnighaus JM, Turner AC, de Cock K, Zuckerman M. Letter on Infection with HIV-1 among leprosy patients in Zaire. Journal of Infectious Diseases 1995; 171: 502-3. 7. Floyd S, Black GF, Dockrell HM, Fine PEM. Analysis of data from individuals demonstrates high discordance between IFN-? assays and PPD-tuberculin skin tests used in screening for tuberculosis infection. (Reply). International Journal of Tuberculosis and Lung Disease 2002; 6: 90. 8. Dockrell HM, Black GF, Weir RE, Fine PEM. Can the efficacy of Bacille Calmette-Guérin tuberculosis vaccine be affected by intestinal parasitic infections? (Reply). Journal of Infectious Diseases 2002; 186: 442-3. III ABSTRACTS 1. Pönnighaus JM, Bliss L, McDougall AC, Fine PEM. The influence of different case definitions on the observed pattern of leprosy in an endemic area in Northern Malawi. Proceedings of the XII International Leprosy Congress, New Delhi, 20-24 February 1984; 656-665. 2. Fine PEM, Pönnighaus JM, Rees RJW, Convit J, Clarkson JA, Bliss L. Epidemiological studies with M leprae soluble antigen skin tests. Proceedings of the XII International Leprosy Congress, New Delhi, 20-24 February 1984; 103-107. 3. Boerrigter FG, McDougall AC, Pönnighaus JM. The value of histopathology in a Leprosy Control Programme. Proceedings of the XII International Leprosy Congress, New Delhi, 20-24 February 1984. 4. McDougall AC, Pönnighaus JM, Fine PEM, Zonena KH. The histopathological examination of skin biopsies form an epidemiological study of leprosy in Northern Malawi. Proceedings of the XII International Leprosy Congress, New Delhi, 20-24 February 1984; 763-765. 5. Pönnighaus JM, Gruer PJK, Fine PEM, Maine N. The anatomical distribution of single leprosy lesions in an African population, and its implications for the pathogenesis of leprosy. Abstracts of the XIII International Leprosy Congress, The Hague, 12-16 September 1988. Quaderni di Cooperazione sanitoria 1988; 9: 23. 6. Boerrigter G, Pönnighaus JM. A new concept of staging paucibacillary leprosy and its application to the analysis of post-treatment results of an MDT study in Malawi. Abstracts of the XIII International Leprosy Congress, The Hague, 12-16 September 1988. Quaderni di Cooperazione sanitoria 1988; 9: 18. 7. Pönnighaus IM, Boerrigter G, Fine PEM, Pönnighaus JM. Disabilities in leprosy patients ascertained in a total population survey in Karonga District, northern Malawi. Abstracts of the XIII Inter-national Leprosy Congress, The Hague, 12-16 September 1988. Quaderni di Cooperazione sanitoria 1988; 9: 60. 8. Fine PEM, Pönnighaus JM, Maine N. The rural-urban paradox in leprosy. Abstracts of the XIII International Leprosy Congress, The Hague, 12-16 September 1988. Quaderni di Cooperazione sanitoria 1988; 9: 139. 9. Bliss L, Pönnighaus JM, Fine PEM. Implications of new technology for data processing in epidemiological studies of leprosy. Abstracts of the XIII International Leprosy Congress, The Hague, 12-16 September 1988. Quaderni di Cooperazione sanitoria 1988; 9: 598. 10. Lucas S, Pönnighaus JM, Ddumba E, Nsubuga P, Dewind C. Dermatopathological aspects of HIV disease in Africa. IVth International Conference on AIDS and Associated Cancers in Africa. 1989 Abstract 164, p 88. 11. Pönnighaus JM, Mwanjasi LJ, Fine PEM, Shaw M, Turner A, Oxborrow SM, Sterne JAC. Is HIV infection a risk factor for leprosy? Abstracts of Fifth International Conference on AIDS in Africa 1990: 86. 12. Pönnighaus JM, Fine PEM, Sterne JAC, Wilson RJ. Incidence rates of leprosy decline with increasing duration of schooling and with improving standards of housing in Karonga District, Northern Malawi. Abstracts of the 14th International Leprosy Congress, Orlando, Florida, 29 August - 4 September 1993; 68A and International Journal of Leprosy 1993; 61(4) Supplement: 68A. 13. Sterne JAC, Pönnighaus JM, Fine PEM, Bliss L. Association of Geographic Factors with Leprosy Incidence Rates in Karonga District, Northern Malawi. Abstracts of the 14th International Leprosy Congress, Orlando, Florida, 29 August - 4 September 1993, 1993; 68A and International Journal of Leprosy, 1993; 61(4) Supplement: 74A. 14. Fine PEM, Sterne JAC, Pönnighaus JM, Bliss L, Rees RJW. The implications of delayed-type hypersensitivity to M Leprae soluble antigens and to tuberculin for natural and vaccine-derived immunity to leprosy. Abstracts of the 14th International Leprosy Congress, Orlando, Florida, 29 August - 4 September 1993, 1993; 68A and International Journal of Leprosy 1993; 61(4) Supplement: 74A. 15. Pönnighaus JM, Gooskens V, Clayton Y, Mkandawire P, Sterne J. Die Behandlung oberflachlicher Mykosen in den Tropen - Ergebnisse einer Doppelblindstudie im Karonga Distrikt / Malawi. Myk '93 27 Wissenschaftliche Tagung Deutsch sprachige Mykologische Gesellschaft. 30 September bis 3 Oktober 1993 in Greifswald. 16. Lucas SB, Fine PEM, Job CK, Meyers WM, Pönnighaus JM, Sterne JAC. Observer variation in the histological diagnosis of leprosy. How important is it? J Pathol 1993; 169: (supplement); 126A 17. Ngwira BM, Warndorff DK, Chagaluka SD, Fine PEM, Lucas SB. Tuberculous lymphadenitis in Karonga District, Malawi. Conference on Global Lung Health and the Annual Meeting of the International Union against Tuberculosis and Lung Disease, Paris, 1-4 October 1997 International Journal of Tuberculosis and Lung Disease 1997; 1(5) Supplement 1: S114 18. Fine PEM, Bruce JC, Vynnycky E, Pönnighaus JM. Patterns of tuberculin conversion and reversion: biology or artefact? Conference on Global Lung Health and the Annual Meeting of the International Union against Tuberculosis and Lung Disease, Paris, 1-4 October 1997 International Journal of Tuberculosis and Lung Disease 1997; 1(5) Supplement 1: S97 19. Warndorff DK, Chagaluka SD, Glynn JR, Yates MD, Pönnighaus JM, Fine PEM. Mycobacteria other than tuberculosis (MOTT), HIV and the diagnosis of TB in Karonga District, Malawi. Conference on Global Lung Health and the Annual Meeting of the International Union against Tuberculosis and Lung Disease, Paris, 1-4 October 1997 International Journal of Tuberculosis and Lung Disease 1997; 1(5) Supplement 1: S150 20. Warndorff DK, Pönnighaus JM, Fine PEM. Deliberations on the early skin lesion in leprosy. Abstracts of the XV International Leprosy Congress, Beijing, 7-12 September 1998. 21. Fine PEM, Floyd S, Sterne J, Pönnighaus JM. Implications of environmental mycobacterial infections for the epidemiology of leprosy. Abstracts of the XV International Leprosy Congress, Beijing, 7-12 September 7-12 1998. 22. Glynn JR, Warndorff DK, Malema SS, Nkhosa P, Bliss L, Turner AC, Fine PEM. Risk factors for tuberculosis (TB) in a rural African population cohort with known HIV status. Abstracts of the XII World AIDS Conference, Geneva, 28 June - 3 July 1998. 23. Black GF, Warndorff DK, Chaguluka SD, Weir R, Dockrell HM, Blackwell J, Fine PEM. Immune responses to mycobacterial antigens in a Malawian population. Abstracts of the X International Congress of Immunology, New Delhi, 1-6 November 1998. 24. Weir RE, FINE PEM, Blackwell JM, Black GF, Jarman E, Dockrell HM. Immunological correlates of protection induced by BCG vaccination: a comparative study between the UK and Malawi. Proceedings of the Fourth International Conference on the Pathogenesis of Mycobacterial Infections, Stockholm July 1999 (Abstract P149). 25. Crampin AC, Sibande F, Mulawa D, Bliss L, Ngwira B, Glynn JR, Fine PEM. Impact of HIV in rural Malawi: 10-year follow-up study. Abstracts of the XI International Conference on AIDS and STDs in Africa, Lusaka, 12-16 September 1999. P. 22. 26. Glynn JR, Abarea K, Clewley JP, Ngwira B, Malema S, Warndorff DK, Crampin AC, Fine PEM. HIV subtypes in Northern Malawi: a pilot study. Abstracts of the XI International Conference on AIDS and STDs in Africa, Lusaka, 12-16 September 1999. P. 44. 27. Ngwira B. Randomised controlled trial of M. vaccae in patients with pulmonary tuberculosis and HIV infection. Abstracts of the 30th IUATLD World Conference on Lung Health, Madrid, 14-18 September 1999. International Journal of Tuberculosis and Lung Disease. 1999; 3(9) Supplement 1: S21 28. Floyd S, Pönnighaus JM, Bliss L, Warndorff DK, Kasunga A, Sifukwe M, Fine PEM. BCG scars in northern Malawi: persistence over time, repeatability of scar reading, and factors affecting scar size. Abstracts of the 30th IUATLD World Conference on Lung Health, Madrid, 14-18 September 1999. International Journal of Tuberculosis and Lung Disease. 1999; 3(9) Supplement 1: S27 29. Fine PEM, Floyd S, Stanford J, Bliss L, Kileta S, Pönnighaus JM. Sensitivity to antigens of non- tuberculous mycobacteria (NTM) in northern Malawi: patterns and implications. Abstracts of the 30th IUATLD World Conference on Lung Health, Madrid, 14-18 September 1999. International Journal of Tuberculosis and Lung Disease. 1999; 3(9) Supplement 1: S28 30. Warndorff DK, Yates M, Ngwira B, Chaguluka S, Jenkins PA, Drobniewski F, Pönnighaus JM, Glynn JR, Fine PEM. Trends in antituberculosis drug resistance in Karonga District Malawi, 1986-1998. Abstracts of the 30th IUATLD World Conference on Lung Health, Madrid, 14-18 September 1999. International Journal of Tuberculosis and Lung Disease. 1999; 3(9) Supplement 1: S163 31. Weir RE, Fine PEM, Blackwell JM, Black GF, King E, Hogg A, Branson K, Bliss L, Floyd S, Dockrell HM. Analysis of the Development of the Protective Immune Response to BCG Vaccination in UK Schoolchildren. Abstracts of the Tuberculosis 2000: Past, Present and Future meeting, New York, 20- 24 June 2000. 32. Black GF, Fine PEM, Warndorff DK, Weir RE, Blackwell JM, Brennan PJ, Terloew S, Sichali L, Chaguluka S, Jarman E, Ngwira B, Bliss L, Floyd S, Dockrell HM. Patterns of cytokine and skin test responsiveness to mycobacterial antigens in healthy, young adults in Northern Malawi before (and after) BCG vaccination. Abstracts of the Tuberculosis 2000: Past, Present and Future meeting, New York, 20-24 June 2000. 33. Fine PEM. BCG: efficacy and immunity. Abstracts of Keystone Symposium : Molecular and cellular aspects of tuberculosis research in the post genome era, Taos, New Mexico 25-30 January 2001. 34. Fitness J, Wallace C, Siddiqui MR, Meisner S, Tosh K, Balakrishnan K, Ghei S, Fisher SE, Golding M, Narayan NPS, Thiagarajan Sitaraman T, Sengupta U, Pitchappan R, Lifted Sichale L, Mwaungulu L, Fine PEM, Hill AVS. A susceptibility locus for leprosy maps to chromosome 10p13 in both India and Malawi. Abstracts of Australasian Gene Mapping conference Cairns, 2001. 35. Crampin AC, Floyd S, Glynn JR, Mwinuka V, Malema SS, Ngwira B, Fine PEM. The role of household and other contacts for tuberculosis risk in Karonga District, Malawi. 27th Tuberculosis Surveillance Research Unit meeting Munchenwiler, Switzerland, April 5-7 2001. 36. Glynn JR, Yates MD, Crampin AC, Ngwira B, Chaguluka S, Drobniewski F, Fine PEM. Molecular epidemiology of TB in Karonga District, Malawi: preliminary findings. 27th Tuberculosis Surveillance Research Unit meeting, Munchenwiler, Switzerland, April 5-7 2001. 37. McCormack GP, Glynn JR, Fine PEM, Clewley JP. Molecular Epidemiology of HIV in Karonga District, Malawi. Abstracts of the 8th annual meeting on HIV Evolution and Diversity Paris, 27-29 April 2001. 38. Zaba B, Crampin AC, Nakiyingi J, Urassa M, Floyd S, Sloggett A. The impact of HIV on child mortality: some results from the UNICEF multi-centre study. Abstracts of the 24th IUSSP General Conference Salvador, Brazil, 18-24 August 2001. 39. Crampin AC, Floyd S, Sibande F, Mulawa D, Broadbent P, Bliss L, Ngwira B, Glynn JR, Fine PEM. Long term follow-up of HIV positive and negative natural history cohorts in rural Malawi. Abstracts of the 24th IUSSP General Conference Salvador, Brazil, 18-24 August 2001 40. Fine PEM. Tuberculosis epidemiology and environmental influences. Abstracts of the 149th ordinary meeting of the Society for General Microbiology University of East Anglia, 10-13 September 2001, P.3- 4. 41. Fine PEM, Black GA, Weir R, Floyd S, Crampin AC, Sichale L, Chaguluka S, Dockrell HM. Exposure to environmental mycobacteria can explain differences in protection by BCG against tuberculosis in Malawi and the UK. Abstracts of the 32nd IUATLD World Conference on Lung Health, Paris, 1-4 November 2001. International Journal of Tuberculosis and Lung Disease. 2001; 5(11) Supplement 1: S19-S20. 42. Floyd S, Bliss L, Ponnighaus JM, Nkhosa P, Sichali L, Msiska G, Fine PEM. Kinetics of tuberculin delayed-type hypersensitivity induced by BCG vaccination in northern Malawi. Abstracts of the 32nd IUATLD World Conference on Lung Health, Paris, 1-4 November 2001. International Journal of Tuberculosis and Lung Disease. 2001; 5(11) Supplement 1: S211. 43. Vynnycky E, Borgdorff MW, van Soolingen D, Fine PEM. The effect of the magnitude and trend in the annual risk of infection on the interpretation of “clustering" of isolates from tuberculosis cases. Abstracts of the 32nd IUATLD World Conference on Lung Health, Paris, 1-4 November 2001. International Journal of Tuberculosis and Lung Disease. 2001; 5(11) Supplement 1: S37. 44. McCormack GP, Glynn JR, Crampin AC, Pönnighaus JM, Sibande F, Nkhosa P, Bliss L, Broadbent P, Abarca K, Fine PEM, Clewley JP. Development of the HIV epidemic in a rural area of Malawi: spread of subtype C. 12th CISMA 9-13 December 2001, Ougadougou, Burkina Faso. 45. Glynn JR, McCormack GP, Ponnighaus J, Crampin AC, Sibande F, Nkhosa P, Bliss L, Broadbent P, Abarca K, Fine PEM, Clewley JP. The role of migration in establishing the HIV epidemic in a rural area of Malawi. 12th CISMA 9-13 December 2001, Ougadougou, Burkina Faso 46. Dockrell HM, Black GF, Weir RE, Floyd S, Randall A, Bliss L, Warndorff DK, Crampin AC, Ngwira B, Sichali L, Nazareth B, Blackwell JM, Branson K, Chaguluka SD, Donovan L, Jarman E, King E, Fine PEM. Is the IFN-? response to PPD a correlate of protection against human tuberculosis? Abstracts of the VIth Elsinore Meeting on Infection Immunity: "Induction and Maintenance of the Immune Response to Infection". Elsinore, Denmark, 17-21 May 2002. 47. Weir RE, Black GF, Nazareth B, Floyd S, Branson K, King E, Stanley C, Fine PEM, Dockrell HM. Cross-reactivity between BCG and environmental mycobacteria revealed in UK schoolchildren: implications for vaccination and definition of correlates of BCG-induced protective immunity. Abstracts of the Fifth International Conference on the Pathogenesis of Mycobacterial Infections, Stockholm, 27-30 June 2002. 48. Crampin AC, Floyd S, Glynn JR, Madise NJ, Nyondo A, Khondowe MM, Njoka CL, Kanyongoloka H, Ngwira B, Zaba B, Fine PEM. The longterm impact of HIV and orphanhood on the mortality and well- being of children in rural Malawi. Abstracts of the XIV International AIDS Conference, Barcelona, 7-12 July 2002. p. 438. 49. McCormack GP, Glynn JR, Crampin AC, Sibande F, Mulawa D, Bliss L, Broadbent P, Abarca K, Pönnighaus JM, Fine PEM, Clewley JP. Evolution of the HIV-1 subtype C epidemic in rural Malawi from 1981-2000. Abstracts of the 9th International Workshop on HIV Dynamics and Evolution, Lake Arrowhead Conference Centre, California, 17-20 July 2002. 50. Karonga Prevention Trial Group. Long term follow-up of The Karonga Prevention Trial: 15 year trends in protection against leprosy and tuberculosis by BCG, repeat BCG, or BCG combined with killed M leprae in northern Malawi. Abstracts of the 16th International Leprosy Congress Salvador, Brazil, 5-9 August 2002, p.72. 51. Dockrell HM, Hussain R, Spencer JS, Black GF, Shahid F, Zafar S, TerLouw S, Chaguluka S, Sichali L, Crampin AC, Fine PEM, Brennan PJ. Human T cell recognition of fractionated antigens from Mycobacterium leprae: potential as diagnostic reagents. Abstracts of the 16th International Leprosy Congress Salvador, Brazil, 5-9 August 2002, p.87. 52. Cooke G, Campbell S, Bellamy R, Lienhardt C, Sow O, Gustafson P, McAdam K, Sichali L, Mwaungulu L, Warndorff DK, Crampin AC, Chaguluka SD, Fine PEM, Beyers N, Hoal van Helden E, van Helden P, Hill A. Identification of susceptibility genes for tuberculosis in southern and west Africans using family- based linkage analysis and linkage disequilibrium mapping. Abstracts of Keystone Symposium “Tuberculosis: integrating host and pathogen biology” Taos, New Mexico, 25-30 January 2003. 53. Black GF, Weir RW, Chaguluka SD, Warndorff DK, Crampin AC, Mwaungulu L, Sichali L, Floyd S, Bliss L, Andersen P, Britton W, Hewinson G, Huygen K, Paulsen J, Singh M, Prestidge R, Fine PEM, Dockrell HM. Interferon-? responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-BCG vaccinated Malawian young adults. Abstracts of Keystone Symposium “Tuberculosis: integrating host and pathogen biology” Taos, New Mexico, 25-30 January 2003. 54. Floyd S, Crampin AC, Glynn JR, Madise N, Nyondo A, Khondowe MM, Njoka CL, Kanyongoloka H, Ngwira B, Fine PEM. The impact of HIV on household structure in rural Malawi. Conference: Empirical evidence for the demographic and socio-economic impact of AIDS Durban, South Africa 26-28 March 2003 (oral) 55. Mwaungulu F, Crampin AC, Zachariah R, Spielmann M-P, Salaniponi F, Harries A. Voluntary counselling and HIV testing plus cotrimoxazole prophylaxis can reduce case fatality rates in patients with tuberculosis in Malawi: from research to policy and practice. Abstracts of the TSRU meeting Bagamoyo, Tanzania, 3-5 April 2003. IV OTHER PUBLISHED REPORTS TO WHICH LEP / KPS HAS CONTRIBUTED DATA 1. Srinivasan H, Stumpe B. Leprosy diagnosis: a device for testing the thermal sensibility of skin lesions in the field. Bulletin of the World Health Organisation 1989; 67: 635-641. 2. Fine PEM. Immunological tools in leprosy control. International Journal of Leprosy 1989; 57: 671-686. 3. de Wit MYL, Faber WR, Krieg SR, Douglas JT, Lucas SB, Montreewasuwat N, Pattyn SR, Hussain R, Pönnighaus JM, Hartskeerl RA, Klatser PR. Application of a Polymerase Chain Reaction for the Detection of Mycobacterium leprae in skin tissues. Journal of Clinical Microbiology 1991; 29 no 5: 906- 910. 4. Pönnighaus JM, contributor to: Methods for field trials of interventions against tropical diseases, a toolbox, edited by PG Smith and Richard H Morrow, Oxford University Press, 1991. 5. Godfrey-Faussett P, Stoker N. Aspects of tuberculosis in Africa 2: Genetic "fingerprinting" for clues to the pathogenesis of tuberculosis. Transactions of the Royal Society of Tropical Medicine and Hygiene 1992; 86: 472-475. 6. Boerrigter G, Pönnighaus JM. Does the introduction of WHO-MDT influence trends in the incidence of leprosy? - the Malawian experience, Leprosy Review 1993; 64: 227-235. 7. Fine PEM. Immunities in and to tuberculosis: implications for pathogenesis and vaccination. In "Tuberculosis: back to the Future", edited by JDH Porter and KPWJ McAdam. John Wiley Pubs, 1994: 53-74. 8. Lienhardt C, Fine PEM. Type 1 reaction, neuritis and disability in leprosy. What is the current epidemiological situation? Leprosy Review 1994; 65: 9-33. 9. Pönnighaus JM. Leprosy: the beginning of an end to a public health problem? Dermatologic Clinics 1995; 13: 525-536. 10. Fine PEM. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 1995; 346: 1339-45. 11. Fine PEM. Primary prevention of leprosy, International Journal of Leprosy, 1996; 64 (supplement): S44- S49. 12. Fine PEM, Smith, PG. Vaccination against leprosy - the view from 1996. Leprosy Review, 1996; 67: 249-252. 13. Maher D, Nunn P. Evaluation and determinants of outcome of tuberculosis treatment. Bulletin of the World Health Organisation, 1998; 76: 307-308. 11 Human Resources

Management Laboratory staff Field Director Dr M Crampin Laboratory Technician Mr H Kanyongoloka Assistant Field Director Dr F Mwaungulu Laboratory Technician Mr KMJ Makamo General Manager Mr R Hartzenberg Laboratory Technician Mr A Mwanyimbo Administrator Mr S Banda Laboratory Technician Mr R Ndhlovu Senior Immunologist Dr A Ben Smith Laboratory Attendant Ms M Thindwa Laboratory Manager Mr R Dacombe Laboratory Attendant Ms J Munthali Medical Epidemiologist Dr A Jahn Technical staff Paediatrician (Clinical Officer) Dr H Mvula Stores Keeper Mr B Chikwezga Senior positions Mechanic Mr KG Msiska Administrative Assistant Mr LED Mponda Mechanic Mr CT Nyirenda Administrative Officer Ms S Chirwa Electrician Mr O Nkhoma Project Secretary Ms JC Mwafulirwa Plumber Mr WM Mzumara Data Manager / Programmer Mr S Kileta Assistant Electrician Mr T Nyirenda Data office administrator Mr A Nyondo Builder Mr RM Gondwe Senior Laboratory Technician Mr S Chaguluka Carpenter Mr J Kaira Senior Interviewer Mr SS Malema Carpenter Mr MK Mwafulirwa Senior Interviewer Mr VK Mwinuka Driver Mr F Simwaba Senior LCA/Paramedic Mr GK Msiska Driver Mr FSC Banda Data office Ancillary staff Data entry supervisor Mr N Kasunga Messenger Mr D Msowoya Coding supervisor Mr P Mogha Messenger Mr R Gondwe Computer Officer Mr T Mtawali Camp Attendant Ms J Munthali Data co-ordinator Mr N Mwaungulu Camp Attendant Mr D Kalambo Coder Mr BJ Mtawali Labourer Mr G Kawonga Coder Mr WL Mwamlima Labourer Mr A Mhango Coder Mr M Mponda Labourer Mr V Kaunda Coder Mr LC Ngwira Labourer Mr P Chigadula Coder Mr GJ Mwafilaso Watchman Mr K Msowoya Coder Mr R Kondowe Watchman Mr LA Nkhoma Computer Operator Ms PG Ngwira Watchman Mr B Gondwe Computer Operator Ms K Mkandawire Watchman Mr J Mzumara Computer programmer (trainee) Ms C Kabaghe Watchman Mr P Mwafulirwa Librarian Mr FO Mwangolowo Watchman Mr M Mwanjawala Assistant Librarian Mr R Mhango Watchman Mr A Mapunda Clinical staff Watchman Mr A Mzumara Radiographer Mr S Mphande Watchman Mr C Nyirenda Research Nurse Ms C Chisambo Watchman Mr R Mwafulirwa Research Nurse Ms L Phiri Watchman Mr L Mwafulirwa Research Nurse Ms JT Mwaungulu Watchman Mr S Msiska Medical Assistant Mr I Nkhoma Watchman Mr G Kasambala Medical Assistant Mr L Kachiwanda Medical Assistant Mr WN Pistoni (1st WT Programme) L C A / Paramedic Mr O Mwanyongo Field Director Dr D Warndorff L C A / Paramedic Mr K Munthali Ass’t Field Director Dr B Ngwira L C A / Paramedic Ms M Kondowe Immunologist Dr G Black L C A / Paramedic Mr D Mulawa L C A / Paramedic Mr WB Sichone Based Elsewhere L C A / Paramedic Mr S Kasimba Mol biologist (CPHL) Dr G McCormack L C A / Paramedic Mr HK Phiri Geneticist (Oxford) Dr J Fitness L C A / Paramedic Mr P Nkhosa Geneticist (Oxford) Dr R Siddiqui L C A / Paramedic Mr HC Jabu L C A / Paramedic Mr DT Mwafulirwa Based at LSHTM: L C A / Paramedic Mr FM Sibande Investigators Prof P Fine L C A / Paramedic Mr LK Sichali Prof H Dockrell Other field staff Ms B Zaba Interviewer Mr T Mhango Immunologist Dr R Weir Interviewer Ms B Kishombe Immunologist Dr P Gorak-Stolinska Interviewer Mr B Mangongo Epidemiologist Dr J Glynn Interviewer Mr G Chiona Laboratory technician Ms Maeve Lalor Interviewer Mr E Mwaiyeghele Statistician Ms S Floyd Interviewer Mr LE Mlenga Systems analyst Ms J Saul Interviewer Mr S Munkhondia Computer specialist Mr K Branson Interviewer Mr M Mwenibabu Research assistant Ms R Blitz Interviewer Mr L Mwaungulu Secretary-administrator Ms L Pollock 2 of our Malawian senior staff are funded to complete an MSc in Epidemiology at LSHTM during the current research programme, KPS is committed to continue to support local staff to assume leadership positions in research and is hoping to extend the allocation of resources for training programmes in the future.