Qualitative and quantitative detection of SARS-CoV-2 RNA in untreated wastewater in Western Cape Province, South Africa.

Recent studies have shown that the detection of SARS-CoV-2 genetic material in wastewater may provide the basis for a surveillance system to track the environmental dissemination of this virus in communities. An effective wastewater-based epidemiology (WBE) system may prove critical in South Africa (SA), where health systems infrastructure, testing capacity, personal protective equipment and human resource capacity are constrained. In this proof-of-concept study, we investigated the potential of SARS-CoV-2 RNA surveillance in untreated wastewater as the basis for a system to monitor COVID-19 prevalence in the population, an early warning system for increased transmission, and a monitoring system to assess the effectiveness of interventions. The laboratory confirmed the presence (qualitative analysis) and determined the RNA copy number of SARS-CoV-2 viral RNA by reverse transcription polymerase chain reaction (quantitative) analysis from 24-hour composite samples collected on 18 June 2020 from five wastewater treatment plants in Western Cape Province, SA. The study has shown that a WBE system for monitoring the status and trends of COVID-19 mass infection in SA is viable, and its development and implementation may facilitate the rapid identification of hotspots for evidence-informed interventions.

Human immunodeficiency virus increases the risk of tuberculosis due to recent re-infection in individuals with latent infection.

BACKGROUND: Human immunodeficiency virus associated tuberculosis (TB) disease can follow reactivation of latent Mycobacterium tuberculosis infection or recent (re-)infection with M. tuberculosis. If contemporary TB cases share identical M. tuberculosis strains (i.e., are 'clustered'), the episode is likely to have followed recent (re-)infection, irrespective of evidence of previous latent infection. METHODS: Individuals experiencing a first TB episode between 1996 and 2008 in Karonga District, Northern Malawi, were included if information on M. tuberculosis infection status (from tuberculin tests) before 1990 and a DNA fingerprint from the TB episode were available. We explored differences in proportion clustered by prior M. tuberculosis infection status and HIV status, adjusting for age, sex, bacille Calmette-Guérin scar status and time since tuberculin testing. RESULTS: Of 79 HIV-negative TB cases, those with previous M. tuberculosis infection were much less likely to be clustered than cases without prior infection (29% vs. 77%, adjusted OR = 0.15, 95%CI 0.04-0.59). Among 119 HIV-positive TB cases, clustering was similar in both groups (88% vs. 84%, adjusted OR = 1.85, 95%CI 0.41-8.29). DISCUSSION: HIV infection appears to increase the risk of TB following recent re-infection in patients with latent M. tuberculosis infection. Our results add to the mounting evidence that HIV-associated TB mainly follows recent M. tuberculosis infection.

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.

Field-based random sampling without a sampling frame: control selection for a case-control study in rural Africa.

Selection bias, particularly of controls, is common in case-control studies and may materially affect the results. Methods of control selection should be tailored both for the risk factors and disease under investigation and for the population being studied. We present here a control selection method devised for a case-control study of tuberculosis in rural Africa (Karonga, northern Malawi) that selects an age/sex frequency-matched random sample of the population, with a geographical distribution in proportion to the population density. We also present an audit of the selection process, and discuss the potential of this method in other settings.

Tuberculosis: associations with HIV and socioeconomic status in rural Malawi.

Tuberculosis (TB) is associated with human immunodeficiency virus (HIV) infection, increasing age and male sex, but less is known about other risk factors in developing countries. As part of the Karonga Prevention Study in northern Malawi, we conducted a retrospective cohort study in the general population to assess risk factors for the development of TB. Individuals were identified in 1986-89 and TB cases diagnosed up to 1996 were included. TB was confirmed in 62/11,059 (0.56%) HIV negative individuals and 7/182 (3.9%) HIV positive individuals (relative risk 7.1, 95% confidence interval 3.2-15.7). This association was little altered by adjustment for age, sex or socioeconomic factors. The risk of TB was higher in those aged over 30 years than in younger individuals, in men than in women, in those engaged in occupations other than farming than in subsistence farmers, in those living in households with burnt brick dwellings than in those with less well built dwellings, and in those with some schooling than in those with none. These associations persisted after adjusting for age, sex, HIV status and population density. The absolute risks of TB were low in this study due to the passive follow-up and strict diagnostic criteria. The relative risk with HIV was of a similar magnitude to that measured elsewhere. Increased risks of TB with age and in men are expected. Associations with measures of higher socioeconomic status were unexpected. They may reflect a greater likelihood of diagnosis in this group.

Geographic determinants of leprosy in Karonga District, Northern Malawi.

BACKGROUND: Geographical differences in leprosy risk are not understood, but may provide clues about the natural history of the disease. We report an analysis of the geographical distribution of leprosy in Karonga District, a rural area of Northern Malawi, between 1979 and 1989. METHODS: Cohort study of the incidence of leprosy based on two total population surveys. Area of residence was determined using aerial photographs, which allowed identification of households, as well as location of roads, rivers and the lake shore. RESULTS: Incidence rates were between two and three times higher in the north compared to the south of the district, and lowest in the semi-urban district capital. The most obvious environmental difference between these regions is the north's higher rainfall and more fertile soil. There was no overall association between leprosy incidence and population density, although highest rates were observed in the least densely populated areas. Looking at the entire district, incidence rates increased with increasing distance from a main road, but declined with increasing distance from a river or from the shore of Lake Malawi. The negative association with proximity to rivers may reflect the larger number of rivers in the north of the district. Apparent differences in incidence rates between groups speaking different languages reflected confounding by area of residence. CONCLUSIONS: There is a marked variation, not explained by socioeconomic or cultural factors, in the incidence of leprosy within Karonga District. Our results are consistent with a theme in the literature associating the environment, particularly proximity to water, with leprosy.

PIP: Researchers do not understand how geographical differences relate to the risk of contracting leprosy. The study of such differences, however, may provide clues about the natural history of the disease. The authors report findings from an analysis of the geographical distribution of leprosy in Karonga District, a rural area in Northern Malawi, between 1979 and 1989. Findings are based data from two total population surveys. The areas of residence were determined using aerial photographs, which allowed the identification of households, roads, rivers, and the lake shore. Analysis revealed that incidence rates were 2-3 times higher in the north compared to the south of the district, and lowest in the semi-urban district capital. The north has higher rainfall and more fertile soil. There was no overall association between the incidence of leprosy and population density, although the highest rates were observed in the least densely populated areas. Considering the entire district, incidence rates increased with increasing distance from a main road, but declined with increasing distance from a river or from the shore of Lake Malawi. This negative association with proximity to rivers may reflect the larger number of rivers in the north of the district. Apparent differences in incidence rates between groups speaking different languages reflected confounding by area of residence. The authors conclude that there is a marked variation, not explained by socioeconomic or cultural factors, in the incidence of leprosy within Karonga District. These results are consistent with literature which associates the environment, especially proximity to water, with leprosy.

Extended schooling and good housing conditions are associated with reduced risk of leprosy in rural Malawi.

Incidence rates of leprosy in Karonga District, northern Malawi, are analyzed by duration of schooling and housing conditions, controlling for age, sex, BCG scar and geographical zone of the household. There is a strong inverse relationship between the number of completed years of schooling and leprosy risk. Good housing conditions are also associated with a decreased risk of developing leprosy in this population. The effect of housing is seen most strongly in young people. It is hypothesized that schooling changes behavior and housing determines environment in ways which are relevant for the transmission of Mycobacterium leprae or for the appropriate priming of the immune system.

Incidence rates of leprosy in Karonga District, northern Malawi: patterns by age, sex, BCG status and classification.

This paper describes incidence rates by age, sex, prior BCG status and classification in Karonga District, northern Malawi. New cases (489) were identified among 83,500 individuals followed for an average of 5 years (1.12 cases per 1000 person years). Only 29 (6%) of the incident cases were multibacillary. Incidence rates generally were higher among females than males, and increased steadily with age. Although the highest incidence rates of disease were recorded among young adults without BCG scars (males 15-19; females 20-24), these peaks were less dramatic than those reported among young adults in The Philippines and Norway. In the absence of historical data and data on infection status, it is not possible to assess to what extent these peaks may reflect either greater exposure or greater susceptibility to disease among adolescents or young adults. The incidence rates of leprosy among individuals with a prior recorded BCG scar were approximately half those of individuals lacking a scar, at all ages. Since BCG had been introduced into this population only during the 1970s, this provides strong evidence for the effectiveness of BCG when given to adults. It was estimated that past vaccination of approximately 40% of the district population had reduced the overall incidence rate of leprosy by 18%, and that this impact would increase with aging of the vaccinated cohorts. A retrospective examination of the detailed records of initial examinations revealed that 62 (13%) of the incidence cases were recorded as having skin hypopigmentation or blemishes, at the site of subsequent confirmed leprosy lesions, several months or years before they were suspected of having leprosy. The nonspecificity of these lesions, some of which were probably attributable to Mycobacterium leprae infection, highlights the difficulty of diagnosing leprosy in its earliest forms.