Process evaluation of a brief messaging intervention to improve diabetes treatment adherence in sub-Saharan Africa.

BACKGROUND: The SMS text Adherence suppoRt for people with type 2 diabetes (StAR2D) intervention is a pragmatic randomised controlled trial, testing the effectiveness of brief text messaging for improving clinical outcomes and medication adherence. The intervention did not impact glycaemic control. We conducted a pre-and post-trial process evaluation alongside the StAR2D study in Malawi and South Africa, exploring the experiences and perceptions of patient participants, to better understand potential underlying reasons for the trial outcomes. METHODS: We employed a qualitative research design, including conducting semi structured in-depth interviews and focus groups at both trial sites. Purposive sampling was used to ensure representation of a wide range of patients with type 2 diabetes with regards to age, gender, ethnicity, language, and duration of diabetes. We interviewed the same participants at baseline and at the end of the trial. We used within-case and across-case thematic analysis to identify key themes. RESULTS: Brief messages delivered by text were acceptable and useful for addressing informational and support needs for participants. Some participants reported behaviour changes because of the text reminders and advice on a healthy lifestyle. Both participating in the trial and the messages were experienced as a source of support, caring, and motivation. Participants' ability to act on the messages was limited. A common theme was frustration over the lack of ability to effectively control one's blood glucose level. They reported a range of routinised, partial diabetes care adherence behaviours, shaped by complex and interacting individual, social, and health service factors. Participant responses and intervention impact were similar across sites, despite differences in health services. CONCLUSION: This process evaluation provided context and insight into the factors influencing participants' engagement with the text messaging intervention. The complex context in which patients take their diabetes medication, may explain in part, why brief text messaging may have been insufficient to bring about changes in health outcomes. The scale of need for self-management and health service support, suggests that health system strengthening, and other forms of self-management support should accompany digital communication interventions. (Current Controlled Trials ISRCTN70768808 , registered 03/08/2015.).

Use of the socio-ecological model to explore factors that influence the implementation of a diabetes structured education programme (EXTEND project) inLilongwe, Malawi and Maputo, Mozambique: a qualitative study.

BACKGROUND: Diabetes Self-Management Education and Support (DSMES) programmes are vital for type 2 diabetes mellitus (T2DM) management. However, they are limited in Sub-Saharan Africa (SSA). To address this gap, a DSMES, namedEXTEND was developed in Lilongwe (Malawi) and Maputo (Mozambique). This qualitative study aimed to explore factors that influence the implementation of DSMES in these settings. METHODS: The Socio-ecological model was applied to explore factors influencing the implementation of DSMES in SSA. Data was analysed using the Framework method and constant comparative techniques. Sixty-six people participated in the study: people with T2DM who participated in the EXTEND programme; healthcare professionals (HCPs), EXTEND educators, EXTEND trainers, and stakeholders. RESULTS: Our findings indicate that there is a need to develop an integrated and dedicated diabetes services in SSA healthcare systems, incorporating culturally adapted DSMES and tailored diabetes training to all professions involved in diabetes management. Traditional media and the involvement of community leaders were proposed as important elements to help engage and promote DSMES programmes in local communities. During the design and implementation of DSMES, it is important to consider individual and societal barriers to self-care. CONCLUSION: Findings from this study suggest that multi-faceted factors play a significant role to the implementation of DSMES programmes in LICs. In the future, EXTEND could be incorporated in the development of diabetes training and dedicated diabetes services in SSA healthcare systems, acting as an educational tool for both people with T2DM and HCPs. This project was supported by the Medical Research Council GCRF NCDs Foundation Awards 2016 Development Pathway Funding.

Digital messaging to support control for type 2 diabetes (StAR2D): a multicentre randomised controlled trial.

BACKGROUND: Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. METHODS: StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. RESULTS: The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (- 0.08% (- 0.31 to 0.16) (IFCC - 0.82 mmol/mol (- 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was - 0.71% (- 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. CONCLUSIONS: Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808.

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients.

OBJECTIVES: To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. METHODS: We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV-positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. RESULTS: We recruited 148 spouses of smear-positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear-positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15-5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV-positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV-positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV-positive community controls. Of 54 HIV-positive spouses, 18 completed 6-month IPT. At 2 year follow-up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34-3.29). CONCLUSIONS: Spouses are a high-risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short-duration therapy.

Declining child mortality in northern Malawi despite high rates of infection with HIV.

OBJECTIVE: To determine whether routine surveys, such as the Demographic and Health Surveys (DHS), have underestimated child mortality in Malawi. METHODS: Rates and causes of child mortality were obtained from a continuous-registration demographic surveillance system (DSS) in Malawi for a population of 32 000. After initial census, births and deaths were reported by village informants and updated monthly by project enumerators. Cause of death was established by verbal autopsy whenever possible. The likely impact of human immunodeficiency virus (HIV) infection on child mortality was also estimated from antenatal clinic surveillance data. Overall and age-specific mortality rates were compared with those from the 2004 Malawi DHS. FINDINGS: Between August 2002 and February 2006, 38 617 person-years of observation were recorded for 20 388 children aged < 15 years. There were 342 deaths. Re-census data, follow-up visits at 12 months of age and the ratio of stillbirths to neonatal deaths suggested that death registration by the DSS was nearly complete. Infant mortality was 52.7 per 1000 live births, under-5 mortality was 84.8 per 1000 and under-15 mortality was 99.1 per 1000. One-fifth of deaths by age 15 were attributable to HIV infection. Child mortality rates estimated with the DSS were approximately 30% lower than those from national estimates as determined by routine surveys. CONCLUSION: The fact that child mortality rates based on the DSS were relatively low in the study population is encouraging and suggests that the low mortality rates estimated nationally are an accurate reflection of decreasing rates.

What has Karonga taught us? Tuberculosis studied over three decades.

This paper summarises tuberculosis (TB) research over almost 30 years in Karonga District, northern Malawi, an area typical of much of rural Africa. The dominant factor has been the human immunodeficiency virus (HIV), which arrived in the district about 1980, leading to an increase in TB incidence to a peak of approximately 65 smear-positive pulmonary cases per 100000 population in 2000. Tuberculin surveys indicate annual risks of Mycobacterium tuberculosis infection of approximately 1%; thus, most of the population is uninfected and at risk of primary infection and disease. Molecular epidemiological studies demonstrate that about two thirds of TB arises from recent infection, but recognisable recent contact is responsible for only about 10% of disease. By 2001, 57% of TB was directly attributable to HIV, implying that it would have declined were it not for HIV. HIV infection increases the risk of TB most among young adults, and greatly increases the risk of recurrence from new infection after treatment. Mortality rates in the HIV-infected are high, but there is no association of HIV with drug resistance. Other risk factors with relatively smaller effects include age and sex, contact, several genetic polymorphisms and area. Neither one nor two doses of the bacille Calmette-Guérin (BCG) vaccine provides protection against adult pulmonary TB, despite protecting against leprosy. Skin test surveys, cohort studies and comparative immunological studies with the UK suggest that exposure to environmental mycobacteria provides some protection against TB and that BCG's failure is attributable partly to this widespread heterologous exposure masking effects of the vaccine. Drug resistance has remained constant (<10%) over more than 20 years. Immunotherapy with M. vaccae provided no benefits, but treatment of HIV-positive patients with cotrimoxazole reduced mortality. The Karonga programme illustrates the value of long-term population-based studies to investigate the natural history of TB and to influence TB control policy. Current studies focus on immunological markers of infection, disease and protection, and on elucidating the impact of antiretroviral treatment on TB incidence at population level.

Herpes simplex virus type 2 trends in relation to the HIV epidemic in northern Malawi.

OBJECTIVES: It is unclear whether the high prevalence of herpes simplex virus type 2 (HSV-2) found in much of Africa predates the HIV epidemic or is, to some extent, a consequence of it. HSV-2 prevalence trends in a rural African community were assessed over a period in which HIV prevalence rose sharply, and antenatal clinic (ANC) surveillance was explored as a method of estimating community HSV-2 prevalence. METHODS: HSV-2 seroprevalence was determined among community controls seen for case-control studies of mycobacterial disease in Karonga district, Malawi, in 1988-90, 1998-2001 and 2002-5, and in women attending ANC as part of surveillance for HIV in 1999-2000. Over this period HIV prevalence rose from 4% to 12%. RESULTS: HSV-2 prevalence in all periods increased sharply with age and was higher in women than in men. After excluding migrants, there was no evidence of change in HSV-2 prevalence in the different periods. Women in the ANC group had lower HSV-2 prevalence than those in the community, but the ANC prevalence was a good approximation to the combined male and female prevalence for the same age group. CONCLUSIONS: This study suggests that HSV-2 was already widespread before the HIV epidemic and has not been greatly influenced by it. It also demonstrates that ANC surveillance may be useful for estimating community HSV-2 prevalence.

Ascertainment of childhood vaccination histories in northern Malawi.

OBJECTIVE: To assess factors related to recorded vaccine uptake, which may confound the evaluation of vaccine impact. METHODS: Analysis of documented vaccination histories of children under 5 years and demographic and socio-economic characteristics collected by a demographic surveillance system in Karonga District, Malawi. Associations between deviations from the standard vaccination schedule and characteristics that are likely to be associated with increased mortality were determined by multivariate logistic regression. RESULTS: Approximately 78% of children aged 6-23 months had a vaccination document, declining to <50% by 5 years of age. Living closer to an under-5 clinic, having a better educated father, and both parents being alive were associated with having a vaccination document. For a small percentage of children, vaccination records were incomplete and/or faulty. Vaccination uptake was high overall, but delayed among children living further from the nearest under-5 clinic or from poorer socio-economic backgrounds. Approximately 9% of children had received their last dose of DPT with or after measles vaccine. These children were from relatively less educated parents, and were more likely to have been born outside the health services. CONCLUSIONS: Though overall coverage in this community was high and variation in coverage according to child or parental characteristics small, there was strong evidence of more timely coverage among children from better socio-economic conditions and among those who lived closer to health facilities. These factors are likely to be strong confounders in the association of vaccinations with mortality, and may offer an alternative explanation for the non-specific mortality impact of vaccines described by other studies.

Assessment and evaluation of contact as a risk factor for tuberculosis in rural Africa.

SETTING: A rural district in Malawi. OBJECTIVE: To determine the effect of inaccurate recall on estimates of the proportion of tuberculosis (TB) cases attributable to contact with identifiable prior cases. DESIGN: Case-control study of laboratory-confirmed TB cases and community controls, comparing family, household and area contacts identified from a database of TB cases with those named at interview. Estimation of prior contact as a risk factor for TB and identified factors associated with being a named contact. RESULTS: Ninety-five per cent of named contacts were known TB cases. The proportion of total identified contacts who were named at interview was 75%, and was similar for cases and controls. Cases were twice as likely as controls to identify prior contacts. Adding database information did not affect odds ratios, but increased the proportion of TB cases attributable to prior contact. Smear-positive, male and human immunodeficiency virus (HIV) negative TB patients were more likely to be named by subsequent cases. Identifiable recent contact with known smear-positive cases accounted for 12.5% of the TB burden. CONCLUSIONS: Reporting of putative source contacts showed little evidence of recall bias and gave estimates of the relative risk of TB associated with identifiable contact. The lower likelihood of HIV-positive cases being named as contacts may reflect reduced infectiousness.

Time delays between patient and laboratory selectively affect accuracy of helminth diagnosis.

Studies of intestinal helminth infections are influenced by the constraints of sample collection, as identification of helminth ova in stools is affected by the time since evacuation from the host. Different methods may be required to optimise diagnostic sensitivity under different study conditions. In the context of studies in rural Malawi, we collected stool samples with different time delays from production by subjects to sample collection by field staff, to examination in the laboratory. Stools were processed by Kato-Katz (KK) or formol-ether concentration (FEC) methods. Hookworm and Schistosoma mansoni were the most common helminths identified. The prevalence of hookworm was higher with KK (270/988, 27%) than with FEC (191/988, 19%). Comparison was made between the results from the two methods according to the timing of the processing steps. Delays in processing did not affect retrieval of S. mansoni. A decrease in sensitivity of almost 50% for detection of hookworm was observed with either method when preservation/refrigeration was delayed by more than 3h. A delay of 1 day from refrigeration or preservation to laboratory processing also reduced the sensitivity for hookworm by 50% for both methods. Care must be taken in studies of multiple helminth infections owing to the selective reduction of hookworm ova during transport. This is particularly critical when samples are not preserved, even over short periods of time, and even with formalin preservation.

Does antiretroviral treatment increase the infectiousness of smear-positive pulmonary tuberculosis?

BACKGROUND: Understanding of the effects of human immunodeficiency virus (HIV) infection and antiretroviral treatment (ART) on Mycobacterium tuberculosis transmission dynamics remains limited. We undertook a cross-sectional study among household contacts of smear-positive pulmonary tuberculosis (TB) cases to assess the effect of established ART on the infectiousness of TB. METHOD: Prevalence of tuberculin skin test (TST) positivity was compared between contacts of index cases aged 2-10 years who were HIV-negative, HIV-positive but not on ART, on ART for <1 year and on ART for 1 year. Random-effects logistic regression was used to take into account clustering within households. RESULTS: Prevalence of M. tuberculosis infection in contacts of HIV-negative patients, HIV-positive patients on ART 1 year and HIV-positive patients not on ART/on ART <1 year index cases was respectively 44%, 21% and 22%. Compared to contacts of HIV-positive index cases not on ART or recently started on ART, the odds of TST positivity was similar in contacts of HIV-positive index cases on ART 1 year (adjusted OR [aOR] 1.0, 95%CI 0.3-3.7). The odds were 2.9 times higher in child contacts of HIV-negative index cases (aOR 2.9, 95%CI 1.0-8.2). CONCLUSIONS: We found no evidence that established ART increased the infectiousness of smear-positive, HIV-positive index cases.

Using tuberculosis suspects to identify patients eligible for antiretroviral treatment.

SETTING: A district in rural sub-Saharan Africa with a recently introduced antiretroviral (ARV) programme. The population has high human immunodeficiency virus (HIV) prevalence and high tuberculosis (TB) incidence. OBJECTIVE: To determine the prevalence of HIV and acquired immune-deficiency syndrome (AIDS) related symptoms in people presenting with chronic cough who are not diagnosed with TB. DESIGN: A cross-sectional survey of TB suspects. METHODS: Patients with chronic cough were recruited from out-patient facilities. After standard diagnostic procedures and providing informed consent, they received counselling and testing for HIV, and were interviewed and examined with respect to staging criteria for HIV/AIDS. Suspects were followed up for 3 months after the end of the recruitment period to allow for delayed diagnosis of TB. RESULTS: Of 145 suspects, 79% had not been diagnosed with TB by the end of the follow-up period. Of these, 108 (95%) agreed to HIV testing and 61 (56%) were HIV-positive. More than half of these were eligible for ARV treatment (Stage III or IV disease) under national programme criteria. CONCLUSION: Established chronic cough clinics are a useful setting for recruitment of patients to ARV clinics. Attendees should be offered HIV testing and simple clinical screening to identify those who should be referred for ARV treatment.

Risk factors for Mycobacterium tuberculosis infection in 2-4 year olds in a rural HIV-prevalent setting.

BACKGROUND: Mycobacterium tuberculosis infection in children acts as a sentinel for infectious tuberculosis. OBJECTIVE: To assess risk factors associated with tuberculous infection in pre-school children. METHOD: We conducted a population-wide tuberculin skin test (TST) survey from January to December 2012 in Malawi. All children aged 2-4 years residing in a demographic surveillance area were eligible. Detailed demographic data, including adult human immunodeficiency virus (HIV) status, and clinical and sociodemographic data on all diagnosed tuberculosis (TB) patients were available. RESULTS: The prevalence of M. tuberculosis infection was 1.1% using a TST induration cut-off of 15 mm (estimated annual risk of infection of 0.3%). The main identifiable risk factors were maternal HIV infection at birth (adjusted OR [aOR] 3.6, 95%CI 1.1-12.2), having three or more adult members in the household over a lifetime (aOR 2.4, 95%CI 1.2-4.8) and living in close proximity to a known case of infectious TB (aOR 1.6, 95%CI 1.1-2.4), modelled as a linear variable across categories (>200 m, 100-200 m, <100 m, within household). Less than 20% of the infected children lived within 200 m of a known diagnosed case. CONCLUSION: Household and community risk factors identified do not explain the majority of M. tuberculosis infections in children in our setting.

Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings.

Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality.

Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area.

To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21-0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time.

The development of the HIV epidemic in Karonga District, Malawi.

OBJECTIVE: To investigate the prevalence and sociodemographic risk factors for HIV infection, during the early stages of the epidemic, in a rural area of northern Malawi. METHODS: As part of a community-based study of mycobacteria, socioeconomic data and HIV results are available on approximately 30,000 individuals from random population samples in 1981-1984 and 1987-1989 from a rural area of Malawi. These have been analysed to characterize the early stages of the HIV epidemic. RESULTS: The earliest HIV-positive specimens were collected in 1982. HIV prevalence in individuals aged 15-49 years was 0.1% in the early 1980s and 2.0% in the late 1980s. In the early 1980s, eight out of 11 HIV-positive individuals were new immigrants to the district or had recently returned there. In the late 1980s, immigration and having spent time outside the district continued to be major risk factors for HIV. HIV infection was more common in those with occupations other than subsistence farming, in those with more schooling, and in those in the best housing. The association with schooling was seen at all ages for both men and women. CONCLUSION: Immigration and travel were important in the repeated introduction and establishment of the HIV epidemic. The association with schooling is similar to that found elsewhere in Africa.

Application of the polymerase chain reaction to the diagnosis of candidosis by amplification of an HSP 90 gene fragment.

A 317-base pair (bp) fragment of the Candida albicans heat shock protein 90 (HSP 90) gene was amplified by the polymerase chain reaction (PCR) for detection of C. albicans DNA in clinical specimens. One hundred specimens were examined including swabs (39), urines (36), peritoneal fluid (9), pus (8) and blood or serum (8): 23% gave positive results with routine culture, 31% with extended broth culture and 37% with PCR. The amplified product was identified by hybridisation with a radiolabelled internal probe and their restriction enzyme digest patterns (SspI, HaeIII, EcoRI, RsaI and XhoI), which could be predicted from the known sequence of HSP 90. C. albicans DNA gave the characteristic 317-bp band and specifically hybridised with restriction enzyme-digested candidal DNA. DNA from other sources intermittently gave multiple faint bands especially in the presence of high concentrations of DNA, but these could be readily distinguished. The method was sensitive to 50 pg of DNA (5 pg with radiolabelled probing) and 100 cfu of C. albicans.

Comparison of two versus three smears in identifying culture-positive tuberculosis patients in a rural African setting with high HIV prevalence.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To compare the sensitivity and specificity of two versus three smears for the diagnosis of pulmonary tuberculosis in a setting with high HIV prevalence. DESIGN: A total of 1992 pulmonary tuberculosis suspects with three sputum smears taken over a 2-7 day period and at least one culture result were studied. Smears were auramine stained and examined using fluorescence microscopy, and positives were confirmed with Ziehl-Neelsen staining and light microscopy. Cultures were set up on Löwenstein-Jensen media. True negative and positive status was defined on the basis of culture. The sensitivity, specificity, and positive and negative predictive values of two and three smears were compared. RESULTS: Compared to culture, the sensitivity, specificity, and positive and negative predictive values of three smears were 70%, 98%, 92%, and 92%, respectively. Restriction to the first two smears gave similar results. Of those detected as smear-positive using three smears, at least 97% would have been detected by two. Among those with HIV serology results available, the sensitivity of two smears for detecting culture-positive tuberculosis was identical to that using three. CONCLUSION: In this setting, using fluorescence and light microscopy, collecting two smears rather than three would only marginally reduce sensitivity and would slightly improve the specificity of diagnosis of tuberculosis; this is unaffected by HIV status. The potential for improving specificity is important because of the costs of misdiagnosis. In practice, both sensitivity and specificity may be increased due to the time saved by examining two rather than three smears.

Tuberculosis and gender: exploring the patterns in a case control study in Malawi.

BACKGROUND: In many populations there is an excess of tuberculosis in young women and older men. We explored possible explanations for these patterns, concentrating on human immunodeficiency virus (HIV) status, pregnancy, smoking, cooking smoke exposure, contact with tuberculosis cases within the household or outside, and gender differences in health service usage and diagnostic delay. DESIGN: Case control study in Karonga District, Malawi. METHODS: Cases were new tuberculosis patients with bacteriological or histological evidence of tuberculosis. Controls were selected in the community using field-based random sampling. RESULTS: The study included 598 tuberculosis cases and 992 controls, with an excess of tuberculosis in young females and older males. This was more marked in HIV-positive individuals. HIV infection was a similarly strong risk factor for tuberculosis in both men and women. Tuberculosis was associated with having a family or household contact with tuberculosis for both men and women. For women, but not men, contacts outside the close family and household were also a risk factor for tuberculosis. Tuberculosis was not associated with current or recent pregnancy, or with smoking or smoke exposure. There were no differences between men and women in health service usage or delay. CONCLUSIONS: In this population, HIV infection and contacts with known tuberculosis patients are important determinants of the gender distribution of cases.