Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana.

OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Impact of pyrethroid resistance on operational malaria control in Malawi

The impact of insecticide resistance on insect-borne disease programs is difficult to quantify. The possibility of eliminating malaria in high-transmission settings is heavily dependent on effective vector control reducing disease transmission rates. Pyrethroids are the dominant insecticides used for malaria control, with few options for their replacement. Their failure will adversely affect our ability to control malaria. Pyrethroid resistance has been selected in Malawi over the last 3 y in the two major malaria vectors Anopheles gambiae and Anopheles funestus, with a higher frequency of resistance in the latter. The resistance in An. funestus is metabolically based and involves the up-regulation of two duplicated P450s. The same genes confer resistance in Mozambican An. funestus, although the levels of up-regulation differ. The selection of resistance over 3 y has not increased malaria transmission, as judged by annual point prevalence surveys in 1- to 4-y-old children. This is true in areas with long-lasting insecticide-treated nets (LLINs) alone or LLINs plus pyrethroid-based insecticide residual spraying (IRS). However, in districts where IRS was scaled up, it did not produce the expected decrease in malaria prevalence. As resistance increases in frequency from this low initial level, there is the potential for vector population numbers to increase with a concomitant negative impact on control efficacy. This should be monitored carefully as part of the operational activities in country.The push for malaria elimination and eventual eradication will be heavily dependent on our ability to reduce disease transmission. A recent editorial suggests that we have the tools to take on this challenge in African malaria heartlands (1). This is predicated on ensuring that vector control prevention and drug treatment tools are fully deployed, reaching every person at risk. There will need to be improved delivery of these tools and better clinical management of malaria cases. In highly endemic areas our ability to reduce malaria transmission will be dependent on vector control, before the focus can shift to killing the parasite in infected people. Two forms of vector control, indoor residual spraying (IRS) and the distribution of long-lasting insecticide-treated nets (LLINs) have been demonstrated to reduce transmission when properly deployed against insecticide susceptible mosquito populations. The use of both interventions has dramatically increased since 2000 in many malaria endemic countries, with increased donor funding to attain the Roll Back Malaria targets and support the malaria elimination agenda (2).IRS and LLINs function by reducing the female mosquito daily survival rate and human biting frequency. Pyrethroids are the only insecticides recommended for use on LLINs, and only four chemical classes of insecticides that attack two target sites are available for IRS, and again pyrethroids dominate the IRS market. Resistance to pyrethroids has been selected in Anopheles gambiae and Anopheles funestus, the major African malaria vectors, although the frequency and level (fold) resistance conferred can vary dramatically. The impact of this resistance on the ability of either control intervention to reduce disease transmission is poorly understood, and current monitoring and evaluation practices are not sufficiently robust to assess this unless catastrophic failures occur. The perceived threat of pyrethroid resistance is now sufficiently high for the World Health Organization (WHO) to convene an international multidonor effort to counteract this.Operationally significant pyrethroid resistance has the potential to limit effective malaria control, owing to the small number of alternative public health insecticides. Pyrethroid resistance in malaria vectors has increased dramatically over the last decade (3, 4), particularly in Africa, where the bulk of malaria-related mortality occurs. Typically resistance is monitored by bioassays, for which the WHO has defined a diagnostic dosage for each insecticide that kills susceptible anopheline mosquitoes (5). Mosquitoes surviving the diagnostic dosage are an indication that resistance has been selected and that an operational problem may be developing, but bioassays alone do not signify control failure.Little operational monitoring of the underlying mechanisms of resistance occurs. Two mechanisms are predominantly responsible for insecticide resistance: changes in the insecticide target site, reducing binding of the insecticide, and increases in the rate at which the insecticide is metabolized (6). Information on the resistance mechanisms is more predictive than bioassays, providing information on the level of resistance and potential cross-resistance between insecticides. For example, two common mutations in the sodium channel convey low-level resistance to pyrethroids and higher-level resistance to dichlorodiphenyltrichloroethane (DDT) in An. gambiae (7, 8), whereas a cytochrome P450-based metabolic regulatory mechanism conveys very high-level pyrethroid and low-level carbamate resistance in An. funestus (9).Vector control interventions are being rapidly scaled up in Malawi, where malaria is highly endemic. Malaria accounts for 34% of all outpatient hospital visits and is the main cause of hospital admissions in children aged <5 y (10). Before 2007 sporadic WHO bioassays were undertaken, which indicated that the two major malaria vectors, An. gambiae and An. funestus, remained fully susceptible to pyrethroids. In 2007 pyrethroid-impregnated LLINs were distributed through antenatal and under-5 clinics at district and central hospitals countrywide. The numbers distributed were sufficient to achieve the Roll Back Malaria targets of 80% of pregnant women and children aged <5 y sleeping under a treated net. In 2008, a pilot study of IRS with the pyrethroid lambda cyhalothrin (ICON, Syngenta) was initiated in Nkhota Khota District, supported by the President’s Malaria Initiative (PMI). The initial program targeted 26,950 houses, and was expanded to 74,772 houses in 2009. Approximately 4 million LLINs were procured and ∼2 million distributed during this time. In 2010 the PMI-supported IRS was expanded to cover the whole of Nkohta Khota district, and the Malawian Ministry of Health supported IRS in a further six districts.A series of sentinel sites were established during this period to track the effect of this rapid increase in insecticide selection pressure on the local vectors and assess any impact on malaria transmission. This was particularly pertinent owing to the high levels of pyrethroid resistance reported in the southern part of neighboring Mozambique in An. funestus, which had prompted a switch from pyrethroids to carbamates or DDT for IRS in the Lubombo Spatial Development Initiative area of Mozambique (11, 12).     

Malaria elimination in Malawi: research needs in highly endemic, poverty-stricken contexts

Malaria control in the impoverished, highly endemic settings of sub-Saharan Africa remains a major public health challenge. Successes have been achieved only where sustained, concerted, multi-pronged interventions have been instituted. As one of the world's poorest countries, Malawi experiences malaria incidence rates that have remained high despite a decade of gradually expanding and more intensive prevention efforts. The Malawi International Center for Excellence in Malaria Research (ICEMR) is beginning work to augment the knowledge base for reducing Plasmodium transmission and malaria morbidity and mortality. Among ICEMR goals, we intend to better assess patterns of infection and disease, and analyze transmission by Anopheles vector species in both urban and rural ecological settings. We will evaluate parasite population genetics and dynamics, transmission intensities and vector ecologies, social and environmental determinants of disease patterns and risk, and human-vector-parasite dynamics. Such context-specific information will help to focus appropriate prevention and treatment activities on efforts to control malaria in Malawi. In zones of intense and stable transmission, like Malawi, elimination poses particularly thorny challenges - and these challengers are different from those of traditional control and prevention activities. Working toward elimination will require knowledge of how various interventions impact on transmission as it approaches very low levels. At present, Malawi is faced with immediate, context-specific problems of scaling-up prevention and control activities simply to begin reducing infection and disease to tolerable levels. The research required to support these objectives is critically evaluated here.     

Former migrant mineworkers with respiratory disease: the South African compensation system, and implications for neighbouring countries

In the region of Southern Africa, substantial numbers of people, primarily males, have been employed in the South African mining industry. Migrant workers from neighbouring countries have constituted a large part of the work force. Until recently, there has been little or no attention directed toward the state of health of these individuals, despite the fact that their work involves a high health risk, especially in regard to mine-related lung diseases. In addition, the South African workers' compensation programme has seldom been utilised by the migrant worker who is a victim of occupational disease. However, recent experiences from Botswana show that compensation claims can be successfully made from the neighbouring countries where the migrant workers originate. Efforts are being made to address the problem systematically, and the government of Botswana is actively involved. The major occupational lung disorders are described briefly, and differential diagnostic problems with pulmonary TB are discussed. Furthermore, a survey of the compensation system in South Africa is presented, and practical steps for medical examinations involving compensation claims are described.     

Prévention et lutte contre le cancer dans la région africaine de l’OMS : un appel à l’action

Cancer is an increasingly significant public health problem worldwide. The majority of new cancer cases and cancer related morbidity and mortality are now occurring in developing countries, especially in Africa. This paper outlines the situation in the WHO African region and describes the priority interventions needed to address the problem. It advocates for the allocation of increased national and international resources for a more equitable access to optimal cancer prevention, diagnosis, care and management. The WHO is committed to supporting capacity-building in Member states with respect to cancer prevention and control and to sharing good practice with respect to integrated approaches to the prevention, treatment and monitoring of cancer and other non-communicable diseases. An impassioned plea for resource mobilization, collaboration and partnership will result in improved cancer prevention and control in Sub-Saharan Africa.     

Implementing safe routes to school: application for the socioecological model and issues to consider

The newly established national Safe Routes to School (SRTS) program has the potential to positively influence individuals, communities, and the environment regardless of race, ethnicity, or socioeconomic status. Many communities are applying their interest in physical activity promotion toward creating policies and programs to encourage active travel, though many barriers exist. SRTS legislation provides funds to address some of the barriers and improve the ability of students to safely walk and bicycle to school. SRTS requires that 70% to 90% of the funds be used for infrastructure projects (i.e., engineering treatments, such as sidewalk construction), and 10% to 30% for noninfrastructure activities, such as education, encouragement, and enforcement. The socioecological model (SEM) is widely used in public health and includes five levels of influence on behavior, from individual to public policy. Application of the SEM to SRTS provides a framework for a comprehensive approach to improve active travel to school.     

Transmission of Mycobacterium tuberculosis among employees in a US government office, Gaborone, Botswana.

SETTING: A US government office located in Botswana where two office employees, one negative and one positive for the human immunodeficiency virus (HIV), were diagnosed with pulmonary tuberculosis (TB) in January 1998. One employee had been symptomatic with untreated laryngeal TB for 8 months. OBJECTIVE: To determine the extent of and risk factors for TB transmission in the office. METHODS: Office contacts were interviewed and a tuberculin skin test (TST) was performed. A positive TST was defined as > or = 10 mm induration for employees from countries where TB is highly endemic, and as > or = 5 mm induration for those from low prevalence counties. RESULTS: Of 79 office contacts investigated, 54/57 (94.7%) born in high TB prevalence countries had a positive TST compared with 4/22 (18.2%) from low prevalence countries (RR 5.1, 95% CI 2.1-12.7, P < 0.001). Of 20 US-born contacts, three (15%) had documented TST conversion, two of whom were co-workers of the employee with laryngeal TB. Isolates of Mycobacterium tuberculosis from the TB cases had matching DNA fingerprints. CONCLUSION: Delayed diagnosis in a setting of high TB prevalence may have contributed to transmission within a US government office located in Botswana. Transmission may have been underestimated due to the high background prevalence of tuberculous infection in the population. Recent tuberculous transmission to persons living with HIV infection may be playing an important role in the escalating TB epidemic in Africa.     

Screening for Antepartum Depression Through Community Health Outreach in Swaziland

Maternal depression, including antepartum and postpartum depression, is a neglected public health issue with potentially far-reaching effects on maternal and child health. We aimed to measure the burden of antepartum depression and identify risk factors among women in a peri-urban community in Swaziland. We conducted a cross-sectional study within the context of a community outreach peer support project involving “Mentor Mothers”. We used of the Edinburgh Postnatal Depression Scale (EPDS) to screen women for depression during the third trimester of pregnancy, using a cut-off score of ≥13 to indicate depression. We also collected demographic and socioeconomic factors, and assessed the association of these factors with EPDS score using logistic regression models. A total of 1038 pregnant women were screened over a period of 9 months. Almost a quarter (22.7 %) had EPDS scores ≥13 and 41.2 % were HIV positive. A fifth, 17.5 % were teenagers and 73.7 % were unemployed. Depression was not associated with HIV status, age or employment status. However, women with multiple socioeconomic stressors were found to be more likely to score highly on the EPDS. Depression was common among pregnant women in the peri-urban areas of Swaziland. Screening for depression using the EPDS is feasible and can be included in the community health worker standard tool box as a way to improve early detection of depression and to highlight the importance of maternal mental health as a core public health concern.