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Background: The COVID-19 pandemic has highlighted the importance of strengthening national monitoring systems to safeguard a globally connected society, especially those in low- and middle-income countries. Africa's rapid adoption of digital technological interventions created a new frontier of digital advancement during crises or pandemics. The use of digital tools for disease surveillance can assist with rapid outbreak identification and response, handling duties such as diagnosis, testing, contact tracing, and risk communication. Malawi was one of the first countries in the region to launch a government-led coordinated effort to harmonize and streamline the necessary COVID-19 digital health implementation through an integrated system architecture., Objective: The aim of this study is to seek expert consensus using the Delphi methodology to examine Malawi's COVID-19 digital surveillance response strategy and to assess the digital tools using the World Health Organization mHealth (mobile health) Assessment and Planning for Scale (MAPS) toolkit., Methods: This protocol follows the Guidance on Conducting and REporting DElphi Studies. Participants must have first-hand experience on the design, implementation or maintenance with COVID-19 digital surveillance systems. There will be no restrictions on the level of expertise or years of experience. The panel will consist of approximately 40 participants. We will use a modified Delphi process whereby rounds 1 and 2 will be hosted online by Qualtrics and round 3 will encompass a face-to-face workshop held in Malawi. Consensus will be defined as ≥70% of participants strongly disagree, disagree, or somewhat disagree, or strongly agree, agree, or somewhat agree. During round 3, the face-to-face workshop, participants will be asked to complete, the MAPS toolkit assessment on the digital tool on which they are experts. The MAPS toolkit will enable the panel members to assess the digital tools from a sustainable perspective from six distinct, yet complementary axes: (1) groundwork, (2) partnerships, (3) financial health, (4) technology and architecture, (5) operations, and (6) monitoring and evaluation., Results: The ability of a country to collate, diagnose, monitor, and analyze data forms the cornerstone of an efficient surveillance system, allowing countries to plan and implement appropriate control actions. Malawi was one of the first countries in the African region to launch a government-led coordinated effort to harmonize and streamline the necessary COVID-19 digital health implementation through an integrated system architecture., Conclusions: We anticipate findings from this Delphi study will provide insights into how and why Malawi was successful in deploying digital surveillance systems. In addition, findings should produce recommendations and guidance for the rapid development, implementation, maintenance, and impact of digital surveillance tools during a health crisis., International Registered Report Identifier (irrid): DERR1-10.2196/58389., (©Alanna Denny, Isaach Ndemera, Kingston Chirwa, Joseph Tsung Shu Wu, Griphin Baxter Chirambo, Simeon Yosefe, Ben Chilima, Matthew Kagoli, Hsin-yi Lee, Kwong Leung Joseph Yu, John O'Donoghue. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 31.12.2024.)

Vaccination is one of the essential measures in reducing transmission, morbidity, and mortality rates of a disease. However, the COVID-19 vaccination is facing hesitancy across the globe, Malawi included. A population-based cross-sectional study was conducted in Malawi to document knowledge, attitudes, and practices on COVID-19 vaccination. The study targeted the general adult population and employed a multi-stage sampling technique. The Census Enumeration Areas within the 16 selected districts served as a primary sampling unit. Among the total 3068 participants, 1947 (63.6%) were female. About 1039 (34.1%) participants had primary education, while only 169 (5.5%) had college education. A total of 2936 (95.7%) participants knew about the COVID-19 vaccine, and 2063 (68.4%) felt that the COVID-19 vaccine was effective. A total of 1180 (38.7%) got vaccinated. Knowledge of the COVID-19 vaccination was significantly associated with participants' education levels, location, occupation, marital status, household family income, and whether they were suffering from chronic illness or not. Overall, the level of knowledge and attitudes about the COVID-19 vaccination was good. This study has also established that different population groups have statistically different levels of knowledge and attitudes regarding COVID-19 vaccination. This study has also indicated a significant relationship between the rate of vaccination and several factors. Therefore, this calls for stakeholders to continue awareness and group-targeted tailored campaigns so as to increase COVID-19 vaccination.

Despite making remarkable strides in improving health outcomes, Malawi faces concerns about sustaining the progress achieved due to limited fiscal space and donor dependency. The imperative for efficient health spending becomes evident, necessitating strategic allocation of resources to areas with the greatest impact on mortality and morbidity. Health benefits packages hold promise in supporting efficient resource allocation. However, despite defining these packages over the last two decades, their development and implementation have posed significant challenges for Malawi. In response, the Malawian government, in collaboration with the Thanzi la Onse Programme, has developed a set of tools and frameworks, primarily based on cost-effectiveness analysis, to guide the design of health benefits packages likely to achieve national health objectives. This review provides an overview of these tools and frameworks, accompanied by other related analyses, aiming to better align health financing with health benefits package prioritization. The paper is organized around five key policy questions facing decision-makers: (i) What interventions should the health system deliver? (ii) How should resources be allocated geographically? (iii) How should investments in health system inputs be prioritized? (iv) How should equity considerations be incorporated into resource allocation decisions? and (v) How should evidence generation be prioritized to support resource allocation decisions (guiding research)? The tools and frameworks presented here are intended to be compatible for use in diverse and often complex healthcare systems across Africa, supporting the health resource allocation process as countries pursue Universal Health Coverage., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

The COVID-19 pandemic has profoundly impacted health systems globally and robust surveillance has been critical for pandemic control, however not all countries can currently sustain community pathogen surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but less is known about the utility of water surveillance of pathogens in low-income countries. Here we show how wastewater surveillance of SAR-CoV-2 can be used to identify temporal changes and help determine circulating variants quickly. In Malawi, a country with limited community-based COVID-19 testing capacity, we explore the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020-May 2022, we collect water from up to 112 river or defunct wastewater treatment plant sites, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predate peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights how wastewater can be used to detect emerging waves, identify variants of concern, and provide an early warning system in settings with no formal sewage systems., (© 2023. The Author(s).)

As the fight against the COVID-19 pandemic continues, reports indicate that the global vaccination rate is still far below the target. Understanding the levels of reinfection may help refocus and inform policymakers on vaccination. This retrospective study in Malawi included individuals and patients who tested for COVID-19 infections via reverse transcriptase polymerase chain reaction (rt-PCR) from the data at the Public Health Institute of Malawi (PHIM). We included all data in the national line list from April 2020 to March 2022. Upon review of 47,032 records, 45,486 were included with a reported 82 (0.18) reinfection representing a rate of 0.55 (95% CI: 0.44-0.68) per 100,000 person-days of follow-up. Most reinfections occurred in the first 90 to 200 days following the initial infection, and the median time to reinfection was 175 days (IQR: 150-314), with a range of 90-563 days. The risk of reinfection was highest in the immediate 3 to 6 months following the initial infection and declined substantially after that, and age demonstrated a significant association with reinfection. Estimating the burden of SARS-CoV-2 reinfections, a specific endurance of the immunity naturally gained, and the role played by risk factors in reinfections is relevant for identifying strategies to prioritise vaccination.

Main Objective: A cohort of adult Malawian people living with HIV (PLHIV) testing positive for cryptococcal antigenemia was observed and followed to determine the outcomes and risk factors for attrition., Methods Concept: Eligible PLHIV were enrolled at 5 health facilities in Malawi, representing different levels of health care. ART naïve patients, ART defaulters returning to care, and patients with suspected or confirmed ART treatment failure with CD4 <200 cells/μL or clinical stage 3 or 4 were enrolled and received CrAg tests on whole blood specimens from August 2018 to August 2019. Hospitalized PLHIV were enrolled and tested for CrAg from January 2019 to August 2019, regardless of CD4 or clinical stage. Patients with cryptococcal antigenemia were managed per Malawian clinical guidelines and were followed up for six months. Survival and risk factors for attrition at six months were assessed., Results: A total of 2146 patients were screened and 112 (5.2%) had cryptococcal antigenemia. Prevalence ranged from 3.8% (Mzuzu Central Hospital) to 25.8% (Jenda Rural Hospital). Of the 112 patients with antigenemia, 33 (29.5%) were diagnosed with concurrent CM at the time of enrollment. Six-month crude survival of all patients with antigenemia (regardless of CM status) ranged from 52.3% (assuming lost-to-follow-up (LTFU) patients died) to 64.9% (if LTFU survived). Patients who were diagnosed with concurrent CM by CSF test had poor survival (27.3-39.4%). Patients with antigenemia who were not diagnosed with concurrent CM had 71.4% (if LTFU died)- 89.8% (if LTFU survived) survival at six months. In adjusted analyses, patients with cryptococcal antigenemia detected after admission to inpatient care (aHR: 2.56, 1.07-6.15) and patients with concurrent CM at the time of positive antigenemia result (aHR: 2.48, 1.04-5.92) had significantly higher hazard of attrition at six months., Conclusions: Overall, our findings indicate a need for routine access to CrAg screening and pre-emptive fluconazole treatment as a way to detect cryptococcal antigenemia and prevent CM in outpatient and inpatient settings. Rapid access to diagnosis and treatment for cryptococcal meningitis (CM) with gold-standard antifungals is needed to improve survival of patients with advanced HIV in Malawi., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The COVID-19 pandemic continues to impact health systems globally and robust surveillance is critical for pandemic control, however not all countries can sustain community surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but little is known about how river and informal sewage in low-income countries can be used for environmental surveillance of SARS-CoV-2. In Malawi, a country with limited community-based COVID-19 testing capacity, we explored the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020 - January 2022, we collected water from up to 112 river or informal sewage sites/month, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predated peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights wastewater can be used for detecting emerging waves, identifying variants of concern and function as an early warning system in settings with no formal sewage systems.

Equitable access and utilization of the COVID-19 vaccine is the main exit strategy from the pandemic. This paper used proceedings from the Second Extraordinary Think-Tank conference, which was held by the Health Economics and Policy Unit at the Kamuzu University of Health Sciences in collaboration with the Malawi Ministry of Health, complemented by a review of literature. We found disparities in COVID-19 vaccine coverage among low-income countries. This is also the case among high income countries. The disparities are driven mainly by insufficient supply, inequitable distribution, limited production of the vaccine in low-income countries, weak health systems, high vaccine hesitancy, and vaccine misconceptions. COVID-19 vaccine inequity continues to affect the entire world with the ongoing risks of emergence of new COVID-19 variants, increased morbidity and mortality and social and economic disruptions. In order to reduce the COVID-19 vaccination inequality in low-income countries, there is need to expand COVAX facility, waive intellectual property rights, transform knowledge and technology acquired into vaccines, and conduct mass COVID-19 vaccination campaigns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kunyenje, Chirwa, Mboma, Ng'ambi, Mnjowe, Nkhoma, Ngwira, Chawani, Chilima, Mitambo, Crampin and Mfutso-Bengo.)

Background: The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the fourth COVID-19 pandemic wave across the southern African region, including Malawi. The seroprevalence of SARS-CoV-2 antibodies and their association with epidemiological trends of hospitalisations and deaths are needed to aid locally relevant public health policy decisions., Methods: We conducted a population-based serosurvey from December 27, 2021 to January 17, 2022, in 7 districts across Malawi to determine the seroprevalence of SARS-CoV-2 antibodies. Serum samples were tested for antibodies against SARS-CoV-2 receptor binding domain using WANTAI SARS-CoV-2 Receptor Binding Domain total antibody commercial enzyme-linked immunosorbent assay (ELISA). We also evaluated COVID-19 epidemiologic trends in Malawi, including cases, hospitalisations and deaths from April 1, 2021 through April 30, 2022, collected using the routine national COVID-19 reporting system. A multivariable logistic regression model was developed to investigate the factors associated with SARS-CoV-2 seropositivity., Findings: Serum samples were analysed from 4619 participants (57% female; 60% aged 18-50 years), of whom 878/3794 (23%) of vaccine eligible adults had received a single dose of any COVID-19 vaccine. The overall assay-adjusted seroprevalence was 83.7% (95% confidence interval (CI), 79.3%-93.4%). Seroprevalence was lowest among children <13 years of age (66%) and highest among adults 18-50 years of age (82%). Seroprevalence was higher among vaccinated compared to unvaccinated participants (1 dose, 94% vs. 77%, adjusted odds ratio 4.89 [95% CI, 3.43-7.22]; 2 doses, 97% vs. 77%, aOR 6.62 [95% CI, 4.14-11.3]). Urban residents were more likely to be seropositive than those from rural settings (91% vs. 78%, aOR 2.76 [95% CI, 2.16-3.55]). There was at least a two-fold reduction in the proportion of hospitalisations and deaths among the reported cases in the fourth wave compared to the third wave (hospitalisations, 10.7% (95% CI, 10.2-11.3) vs. 4.86% (95% CI, 4.52-5.23), p < 0.0001; deaths, 3.48% (95% CI, 3.18-3.81) vs. 1.15% (95% CI, 1.00-1.34), p < 0.0001)., Interpretation: We report reduction in proportion of hospitalisations and deaths from SARS-CoV-2 infections during the Omicron variant dominated wave in Malawi, in the context of high SARS-CoV-2 seroprevalence and low COVID-19 vaccination coverage. These findings suggest that COVID-19 vaccination policy in high seroprevalence settings may need to be amended from mass campaigns to targeted vaccination of reported at-risk populations., Funding: Supported by the Bill and Melinda Gates Foundation (INV-039481)., Competing Interests: All authors declare no conflict of interest., (© 2022 The Author(s).)

Environmental surveillance of rivers and wastewater for SARS-CoV-2 detection has been explored as an innovative way to surveil the pandemic. This study estimated the economic costs of conducting wastewater-based environmental surveillance for SARS-CoV-2 to inform decision making if countries consider continuing these efforts. We estimated the cost of two SARS-CoV-2 environmental surveillance pilot studies conducted in Blantyre, Malawi, and Kathmandu, Nepal. The cost estimation accounted for the consumables, equipment, and human resource time costs used for environmental surveillance from sample selection until pathogen detection and overhead costs for the projects. Costs are reported in 2021 US$ and reported as costs per month, per sample and person per year. The estimated costs for environmental surveillance range from $6,175 to $8,272 per month (Blantyre site) and $16,756 to $30,050 (Kathmandu site). The number of samples processed per month ranged from 84 to 336 at the Blantyre site and 96 to 250 at the Kathmandu site. Consumables costs are variable costs influenced by the number of samples processed and are a large share of the monthly costs for ES (ranging from 39% to 72%). The relatively higher costs per month for the Kathmandu site were attributable to the higher allocation of dedicated human resources and equipment to environmental surveillance for SARS-CoV-2 compared to the Blantyre site where these resources were shared with other activities. The average cost per sample ranged from $25 to $74 (Blantyre) and $120 to $175 (Kathmandu). There were associated economies of scale for human resources and equipment costs with increased sample processing and sharing of resources with other activities. The cost per person in the catchment area per year ranged from $0.07 to $0.10 in Blantyre and $0.07 to $0.13 in Kathmandu. Environmental surveillance may be a low-cost early warning signal for SARS-CoV-2 that can complement other SARS-CoV2 monitoring efforts., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 Ngwira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health technology assessment (HTA) offers a set of analytical tools to support health systems' decisions about resource allocation. Although there is increasing interest in these tools across the world, including in some middle-income countries, they remain rarely used in low-income countries (LICs). In general, the focus of HTA is narrow, mostly limited to assessments of efficacy and cost-effectiveness. However, the principles of HTA can be used to support a broader series of decisions regarding new health technologies. We examine the potential for this broad use of HTA in LICs, with a focus on Malawi. We develop a framework to classify the main decisions on health technologies within health systems. The framework covers decisions on identifying and prioritizing technologies for detailed assessment, deciding whether to adopt an intervention, assessing alternative investments for implementation and scale-up, and undertaking further research activities. We consider the relevance of the framework to policymakers in Malawi and we use two health technologies as examples to investigate the main barriers and enablers to the use of HTA methods. Although the scarcity of local data, expertise, and other resources could risk limiting the operationalisation of HTA in LICs, we argue that even in highly resource constrained health systems, such as in Malawi, the use of HTA to support a broad range of decisions is feasible and desirable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramponi, Twea, Chilima, Nkhoma, Kazanga Chiumia, Manthalu, Mfutso-Bengo, Revill, Drummond and Sculpher.)

Background and Objectives: Pain is common among older persons and has been documented as an important predictor of disability, health, and economic outcomes. Evidence about its prevalence and relationship to well-being is scarce in rural sub-Saharan Africa (SSA), where work is frequently physically demanding, and pain prevention or treatment options are limited. We investigate the prevalence of pain and its association with mental health and subjective well-being in a population-based study of older adults in rural Malawi., Research Design and Methods: We estimate the prevalence, severity, and duration of pain along with its sociodemographic distribution in a sample of 1,577 individuals aged 45 and older. We assess the association of pain with clinically validated measures of mental health, including depression and anxiety, and subjective well-being., Results: Pain is widespread in this mature population with an average age of 60 years: 62% of respondents report the experience of at least minor pain during the last year, and half of these cases report severe or disabling pain. Women are more likely to report pain than men. Pain is a strong predictor of mental health and subjective well-being for both genders. More severe or longer pain episodes are associated with worse mental states. Individuals reporting pain are more likely to suffer from depression or express suicidal thoughts., Discussion and Implications: Our study identifies key subpopulations such as older women in a SSA low-income context who are particularly affected by the experience of pain in daily life and calls for interventions targeting pain and its consequences for mental health and subjective well-being., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Selenium (Se) is an essential human micronutrient. Deficiency of Se decreases the activity of selenoproteins and can compromise immune and thyroid function and cognitive development, and increase risks from non-communicable diseases. The prevalence of Se deficiency is unknown in many countries, especially in sub-Saharan Africa (SSA). Here we report that the risk of Se deficiency in Malawi is large among a nationally representative population of 2,761 people. For example, 62.5% and 29.6% of women of reproductive age (WRA, n = 802) had plasma Se concentrations below the thresholds for the optimal activity of the selenoproteins glutathione peroxidase 3 (GPx3; <86.9 ng mL -1 ) and iodothyronine deiodinase (IDI; <64.8 ng mL -1 ), respectively. This is the first nationally representative evidence of widespread Se deficiency in SSA. Geostatistical modelling shows that Se deficiency risks are influenced by soil type, and also by proximity to Lake Malawi where more fish is likely to be consumed. Selenium deficiency should be quantified more widely in existing national micronutrient surveillance programmes in SSA given the marginal additional cost this would incur.

Background: Research participant remuneration has been variable and inconsistent world-wide for many years owing to uncertainty regarding best practice and a lack of written guidelines for investigators and research ethics committees.  Recent recommendations are that researchers and regulators should develop regionally appropriate written guidelines to define reasonable remuneration based on expense reimbursement, compensation for time and burden associated with participation.   Incentives to motivate participation are acceptable in specific circumstances. Methods: We wished to develop regionally informed, precise and applicable guidelines in Malawi that might also be generally useful for African researchers and review committees.  We therefore reviewed the current literature and developed widely applicable and specific remuneration tables using acceptable and evidence-based payment rationales. Results: There were good international guidelines and limited published regional guidelines.  There were published examples of best practice and sufficient material to suggest a structured remuneration table.  The rationale and method for the table were discussed at an inter-disciplinary workshop resulting in a reimbursement and compensation model with fixed rates.  Payment is recommended pro rata and equally across a study. Conclusions: Transparent, fair remuneration of research participants is recommended by researchers and regulators in Malawi.  The means to achieve this are now presented in the Malawi research participant remuneration table., Competing Interests: Competing interests: Stephen Gordon: As a member of the research community in Malawi, I have an interest that best practice is followed and that was the motivation to organize the workshop. Having organised the workshop, I wanted the findings to be as widely available and discussed as possible.

Aflatoxin-lysine (AFB 1 -lys) adduct levels in blood samples collected from 230 individuals living in three districts of Malawi (Kasungu, Mchinji, and Nkhotakota) and aflatoxin B 1 (AFB 1 ) levels in groundnut and maize samples collected from their respective homesteads were determined using indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) methods. AFB 1 -lys adducts were detected in 67% of blood samples, with a mean concentration of 20.5 ± 23.4 pg/mg of albumin. AFB 1 was detected in 91% of groundnut samples and in 70% of maize samples, with mean AFB 1 levels of 52.4 and 16.3 μg/kg, respectively. All participants of this study reported consuming maize on a daily basis and consuming groundnuts regularly (mean consumption frequency per week: 3.2 ± 1.7). According to regression analysis, a frequency of groundnut consumption of more than four times per week, being female, and being a farmer were significant (p < 0.05) contributors to elevated AFB 1 -lys adduct levels in the blood. This is the first report on AFB 1 -lys adducts in blood samples of residents in Malawi. The results reinforce the urgent need for interventions, aiming at a reduction of aflatoxin exposure of the population.

On May 2, 2009 an outbreak of typhoid fever began in rural villages along the Malawi-Mozambique border resulting in 748 illnesses and 44 deaths by September 2010. Despite numerous interventions, including distribution of WaterGuard (WG) for in-home water treatment and education on its use, cases of typhoid fever continued. To inform response activities during the ongoing Typhoid outbreak information on knowledge, attitudes, and practices surrounding typhoid fever, safe water, and hygiene were necessary to plan future outbreak interventions. In September 2010, a survey was administered to female heads in randomly selected households in 17 villages in Neno District, Malawi. Stored household drinking water was tested for free chlorine residual (FCR) levels using the N,N diethyl-p-phenylene diamine colorimetric method (HACH Company, Loveland, CO, USA). Attendance at community-wide educational meetings was reported by 56% of household respondents. Respondents reported that typhoid fever is caused by poor hygiene (77%), drinking unsafe water (49%), and consuming unsafe food (25%), and that treating drinking water can prevent it (68%). WaterGuard, a chlorination solution for drinking water treatment, was observed in 112 (56%) households, among which 34% reported treating drinking water. FCR levels were adequate (FCR ≥ 0.2 mg/L) in 29 (76%) of the 38 households who reported treatment of stored water and had stored water available for testing and an observed bottle of WaterGuard in the home. Soap was observed in 154 (77%) households, among which 51% reported using soap for hand washing. Educational interventions did not reach almost one-half of target households and knowledge remains low. Despite distribution and promotion of WaterGuard and soap during the outbreak response, usage was low. Future interventions should focus on improving water, sanitation and hygiene knowledge, practices, and infrastructure. Typhoid vaccination should be considered.

Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article.

Introduction: The antiretroviral therapy (ART) programme supported by Médecins Sans Frontières in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district., Methods: A cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL., Results: Of 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load ≤ 1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5)., Conclusions: This study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings.

Background: Malawi has a high burden of infectious disease. The expansion of programmes targeting these diseases requires a strong laboratory infrastructure to support both diagnosis and treatment., Objectives: To assess the use of laboratory test results in patient management and to determine the requirements for improving laboratory services., Methods: A cross-sectional study was conducted in 2012 to survey practising clinicians. Two hospitals were purposively selected for observations of clinicians ordering laboratory tests. Twelve management-level key informants were interviewed. Descriptive statistics were conducted., Results: A total of 242 clinicians were identified and 216 (89%) were interviewed. Of these, 189 (87%) reported doubting laboratory test results at some point. Clinicians most often doubted the quality of haematology (67%), followed by malaria (53%) and CD4 (22%) test results. A total of 151 (70%) clinicians reported using laboratory tests results in patient management. Use of laboratory test results at all times in patient management varied by the type of health facility ( P < 0.001). Ninety-one percent of clinicians reported that laboratories required infrastructure improvement. During 97 observations of clinicians' use of laboratory test results, 80 tests were ordered, and 73 (91%) of these were used in patient management. Key informants reported that the quality of laboratory services was good and useful, but that services were often unavailable., Conclusion: Gaps in the public laboratory system were evident. Key recommendations to enhance the use of laboratory test results in patient management were to strengthen the supply chain, reduce turn-around times, improve the test menu and improve the laboratory infrastructure.

Background: The resistance of malaria parasites to sulphadoxine-pyrimethamine (SP) in 2007 led to the Malawi Ministry of Health changing to artemether-lumefantrine (AL) as first-line for uncomplicated malaria treatment. This study determined the efficacy and safety of AL for the treatment of uncomplicated Plasmodium falciparum malaria among six to 59 months old Malawian children., Methods: This was a prospective study of children six to 59 months old treated with AL after presenting with uncomplicated malaria in the six health facilities in Malawi. The children were followed up on days 1, 2, 3, 7, 14, 21 and 28 days post-treatment and assessed for clinical and parasitological responses. The Kaplan Meier survival estimate was used to measure the efficacy of AL by calculating the cumulative risk of failure at day 28., Results: A total of 322 children were recruited into the study across the six sites. The overall intention-to-treat (ITT) polymerase chain reaction (PCR)-corrected cure rate was 93.4%. Per protocol overall PCR-corrected cure rates for the study sites were; Karonga 98.0%, Kawale 97.4%, Machinga 90.2%, Mangochi 95.4% and Rumphi 91.3%. Nkhotakota study site had the lowest cure rate of 78.0%., Conclusions: There is evidence of good efficacy of AL in Malawi notwithstanding geographical contrasts and this supports the continued use of AL as the first-line treatment for uncomplicated malaria. However there may be need to further investigate the comparatively low efficacy rate found in Nkhotakota district in order to identify possible determinants of treatment failure.

The Malawi Longitudinal Study of Families and Health (MLSFH) is one of very few long-standing, publicly available longitudinal cohort studies in a sub-Saharan African (SSA) context. It provides a rare record of more than a decade of demographic, socioeconomic and health conditions in one of the world's poorest countries. The MLSFH was initially established in 1998 to study social network influences on fertility behaviours and HIV risk perceptions, and over time the focus of the study expanded to include health, sexual behaviours, intergenerational relations and family/household dynamics. The currently available data include MLSFH rounds collected in 1998, 2001, 2004, 2006, 2008, 2010 and 2012 for up to 4000 individuals, providing information about socioeconomic and demographic characteristics, sexual behaviours, marriage, household/family structure, risk perceptions, social networks and social capital, intergenerational relations, HIV/AIDS and other dimensions of health. The MLSFH public use data can be requested on the project website: http://www.malawi.pop.upenn.edu/., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Today's uncertain HIV funding landscape threatens to slow progress towards treatment goals. Understanding the costs of antiretroviral therapy (ART) will be essential for governments to make informed policy decisions about the pace of scale-up under the 2013 WHO HIV Treatment Guidelines, which increase the number of people eligible for treatment from 17.6 million to 28.6 million. The study presented here is one of the largest of its kind and the first to describe the facility-level cost of ART in a random sample of facilities in Ethiopia, Malawi, Rwanda, South Africa and Zambia., Methods & Findings: In 2010-2011, comprehensive data on one year of facility-level ART costs and patient outcomes were collected from 161 facilities, selected using stratified random sampling. Overall, facility-level ART costs were significantly lower than expected in four of the five countries, with a simple average of $208 per patient-year (ppy) across Ethiopia, Malawi, Rwanda and Zambia. Costs were higher in South Africa, at $682 ppy. This included medications, laboratory services, direct and indirect personnel, patient support, equipment and administrative services. Facilities demonstrated the ability to retain patients alive and on treatment at these costs, although outcomes for established patients (2-8% annual loss to follow-up or death) were better than outcomes for new patients in their first year of ART (77-95% alive and on treatment)., Conclusions: This study illustrated that the facility-level costs of ART are lower than previously understood in these five countries. While limitations must be considered, and costs will vary across countries, this suggests that expanded treatment coverage may be affordable. Further research is needed to understand investment costs of treatment scale-up, non-facility costs and opportunities for more efficient resource allocation.

Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to "bad wind," and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak., (© The American Society of Tropical Medicine and Hygiene.)

Dietary micronutrient deficiencies (MNDs) are widespread, yet their prevalence can be difficult to assess. Here, we estimate MND risks due to inadequate intakes for seven minerals in Africa using food supply and composition data, and consider the potential of food-based and agricultural interventions. Food Balance Sheets (FBSs) for 46 countries were integrated with food composition data to estimate per capita supply of calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn), and also phytate. Deficiency risks were quantified using an estimated average requirement (EAR) 'cut-point' approach. Deficiency risks are highest for Ca (54% of the population), followed by Zn (40%), Se (28%) and I (19%, after accounting for iodized salt consumption). The risk of Cu (1%) and Mg (<1%) deficiency are low. Deficiency risks are generally lower in the north and west of Africa. Multiple MND risks are high in many countries. The population-weighted mean phytate supply is 2770 mg capita(-1) day(-1). Deficiency risks for Fe are lower than expected (5%). However, 'cut-point' approaches for Fe are sensitive to assumptions regarding requirements; e.g. estimates of Fe deficiency risks are 43% under very low bioavailability scenarios consistent with high-phytate, low-animal protein diets. Fertilization and breeding strategies could greatly reduce certain MNDs. For example, meeting HarvestPlus breeding targets for Zn would reduce dietary Zn deficiency risk by 90% based on supply data. Dietary diversification or direct fortification is likely to be needed to address Ca deficiency risks., (© 2013 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

Background: The objective of these analyses is to document the relationship between biomarker-based indicators of health and socioeconomic status (SES) in a low-income African population where the cumulative effects of exposure to multiple stressors on physiological functions and health in general are expected to be highly detrimental for the well-being of individuals., Methods: Biomarkers were collected subsequent to the 2008 round of the Malawi Longitudinal Study of Families and Health (MLSFH), a population-based study in rural Malawi, including blood lipids (total cholesterol, LDL, HDL, ratio of total cholesterol to HDL), biomarkers of renal and liver organ function (albumin and creatinine) and wide-range C-reactive protein (CRP) as a non-specific biomarker for inflammation. These biomarkers represent widely used indicators of health that are individually or cumulatively recognized as risk factors for age-related diseases among prime-aged and elderly individuals. Quantile regressions are used to estimate the age-gradient and the within-day variation of each biomarker distribution. Differences in biomarker levels by socioeconomic status are investigated using descriptive and multivariate statistics., Results: Overall, the number of significant associations between the biomarkers and socioeconomic measures is very modest. None of the biomarkers significantly varies with schooling. Except for CRP where being married is weakly associated with lower risk of having an elevated CRP level, marriage is not associated with the biomarkers measured in the MLSFH. Similarly, being Muslim is associated with a lower risk of having elevated CRP but otherwise religion does not predict being in the high-risk quartiles of any of the MLSFH biomarkers. Wealth does not predict being in the high-risk quartile of any of the MLSFH biomarkers, with the exception of a weak effect on creatinine. Being overweight or obese is associated with increased likelihood of being in the high-risk quartile for cholesterol, Chol/HDL ratio, and LDL., Conclusions: The results provide only weak evidence for variation of the biomarkers by socioeconomic indicators in a poor Malawian context. Our findings underscore the need for further research to understand the determinants of health outcomes in a poor low-income context such as rural Malawi.

Selenium (Se) is an essential human micronutrient with critical roles in immune functioning and antioxidant defence. Estimates of dietary Se intakes and status are scarce for Africa although crop surveys indicate deficiency is probably widespread in Malawi. Here we show that Se deficiency is likely endemic in Malawi based on the Se status of adults consuming food from contrasting soil types. These data are consistent with food balance sheets and composition tables revealing that >80% of the Malawi population is at risk of dietary Se inadequacy. Risk of dietary Se inadequacy is >60% in seven other countries in Southern Africa, and 22% across Africa as a whole. Given that most Malawi soils cannot supply sufficient Se to crops for adequate human nutrition, the cost and benefits of interventions to alleviate Se deficiency should be determined; for example, Se-enriched nitrogen fertilisers could be adopted as in Finland.

Background: Zinc deficiency is often associated with nutritional iron deficiency (ID), and may be exacerbated by low selenium status., Aim: To investigate risk of iron and zinc deficiency in women with contrasting selenium status., Methods: In a cross-sectional study, 1-day diet composites and blood samples were collected from self-selected Malawian women aged 18-50 years from low- (Zombwe) (n=60) and high-plant-available soil selenium (Mikalango) (n=60) districts. Diets were analyzed for trace elements and blood for biomarkers., Results: Zinc deficiency (>90 %) was greater than ID anemia (6 %), or ID (5 %), attributed to diets low in zinc (median 5.7 mg/day) with high phytate:zinc molar ratios (20.0), but high in iron (21.0 mg/day) from soil contaminant iron. Zombwe compared to Mikalango women had lower (p<0.05) intakes of selenium (6.5 vs. 55.3 µg/day), zinc (4.8 vs. 6.4 mg/day), iron (16.6 vs. 29.6 mg/day), lower plasma selenium (0.72 vs. 1.60 µmol/L), and higher body iron (5.3 vs. 3.8 mg/kg), although plasma zinc was similar (8.60 vs. 8.87 µmol/L). Body iron and plasma zinc were positive determinants of hemoglobin., Conclusion: Risk of zinc deficiency was higher than ID and was shown not to be associated with selenium status. Plasma zinc was almost as important as body iron as a hemoglobin determinant.

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention.

Since 2004, the Malawi antiretroviral treatment (ART) program has provided a public health-focused system based on World Health Organization clinical staging, standardized first-line ART regimens, limited laboratory monitoring, and no patient-level monitoring of human immunodeficiency virus drug resistance (HIVDR). The Malawi Ministry of Health conducts periodic evaluations of HIVDR development in prospective cohorts at sentinel clinics. We evaluated viral load suppression, HIVDR, and factors associated with HIVDR in 4 ART sites at 12-15 months after ART initiation. More than 70% of patients initiating ART had viral suppression at 12 months. HIVDR prevalence (6.1%) after 12 months of ART was low and largely associated with baseline HIVDR. Better follow-up, removal of barriers to on-time drug pickups, and adherence education for patients 16-24 years of age may further prevent HIVDR.

Background: Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border., Methods: The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE)., Results: We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE., Conclusions: The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Unlabelled: Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01&#95;AE, 25.9% subtype C, 13.1% CRF02&#95;AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06&#95;CPX, CRF07&#95;BC and CRF09&#95;CPX., Conclusions: The optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible for RLS where HIVDR surveillance is recommended to minimize the development and transmission of HIVDR.

Background: There is a worldwide need for a pediatric HIV-1 diagnostic test that has a high diagnostic accuracy, is technically simple and cost efficient. The Up24 HIV-1 assay, which requires both the HIV-1 p24 ELISA and the ELAST signal amplification kit, has previously been shown to be a robust tool to diagnose pediatric HIV-1 from dried whole blood spots (DBS) (Cachafeiro et al., JCM 2009;47:459-62(13)). In order to make the assay more accessible to a resource-limited clinical setting, we eliminated the ELAST system, which simplified the Up24 assay, reduced its cost, and tested the accuracy of the modified assay in a rural Malawian hospital., Objectives: In this proof of concept study, we tested the ability of a simplified Up24 antigen assay, without ELAST, to detect HIV-1 on DBS obtained via heel prick from 6-week-old Malawian infants., Study Design: A case-control study of DBS collected from 113 HIV-infected and 109 HIV-negative infants, using the HIV-1 DNA PCR assay as the reference standard., Results: The simplified HIV-1 Up24 assay had a sensitivity and specificity of 84% and 98%, respectively. When HIV-1 prevalence is 15%, the positive- and negative-predictive values are 89% and 97%, respectively., Conclusion: The simplified Up24 assay has a good positive- and a robust negative-predictive values, is easier to perform and has a reduced cost compared to both HIV DNA PCR and Up24 assays. With additional testing, the simplified Up24 assay has the potential to increase global access to pediatric HIV-1 diagnostics., (Copyright © 2010 Elsevier B.V. All rights reserved.)

As antiretroviral therapy (ART) is scaled up in resource-limited countries, surveillance for HIV drug resistance (DR) is vital to ensure sustained effectiveness of first-line ART. We have developed and applied a broadly sensitive dried-blood-spot (DBS)-based genotyping assay for surveillance of HIV-1 DR in international settings. In 2005 and 2006, 171 DBS samples were collected under field conditions from newly diagnosed HIV-1-infected individuals from Malawi (n = 58), Tanzania (n = 60), and China (n =53). In addition, 30 DBS and 40 plasma specimens collected from ART patients in China and Cameroon, respectively, were also tested. Of the 171 DBS analyzed at the protease and RT regions, 149 (87.1%) could be genotyped, including 49 (81.7%) from Tanzania, 47 (88.7%) from China, and 53 (91.4%) from Malawi. Among the 70 ART patient samples analyzed, 100% (30/30) of the Chinese DBS and 90% (36/40) of the Cameroonian plasma specimens were genotyped, including 8 samples with a viral load of <400 copies/ml. The results of phylogenetic analyses indicated that the subtype, circulating recombinant form (CRF), and unique recombinant form (URF) distribution was as follows: 73 strains were subtype C (34%), 37 were subtype B (17.2%), 24 each were CRF01&#95;AE or CRF02&#95;AG (11.2% each), 22 were subtype A1 (10.2%), and 9 were unclassifiable (UC) (4.2%). The remaining samples were minor strains comprised of 6 that were CRF07&#95;BC (2.8%), 5 that were CRF10&#95;CD (2.3%), 3 each that were URF&#95;A1C and CRF08&#95;BC (1.4%), 2 each that were G, URF&#95;BC, and URF&#95;D/UC (0.9%), and 1 each that were subtype F1, subtype F2, and URF&#95;A1D (0.5%). Our results indicate that this broadly sensitive genotyping assay can be used to genotype DBS collected from areas with diverse HIV-1 group M subtypes and CRFs. Thus, the assay is likely to become a useful screening tool in the global resistance surveillance and monitoring of HIV-1 where multiple subtypes and CRFs are found.

Background: Malaria rapid diagnostics tests (RDTs) can increase availability of laboratory-based diagnosis and improve the overall management of febrile patients in malaria endemic areas. In preparation to scale-up RDTs in health facilities in Malawi, an evaluation of four RDTs to help guide national-level decision-making was conducted., Methods: A cross sectional study of four histidine rich-protein-type-2- (HRP2) based RDTs at four health centres in Blantyre, Malawi, was undertaken to evaluate the sensitivity and specificity of RDTs, assess prescriber adherence to RDT test results and explore operational issues regarding RDT implementation. Three RDTs were evaluated in only one health centre each and one RDT was evaluated in two health centres. Light microscopy in a reference laboratory was used as the gold standard., Results: A total of 2,576 patients were included in the analysis. All of the RDTs tested had relatively high sensitivity for detecting any parasitaemia [Bioline SD (97%), First response malaria (92%), Paracheck (91%), ICT diagnostics (90%)], but low specificity [Bioline SD (39%), First response malaria (42%), Paracheck (68%), ICT diagnostics (54%)]. Specificity was significantly lower in patients who self-treated with an anti-malarial in the previous two weeks (odds ratio (OR) 0.5; p-value < 0.001), patients 5-15 years old versus patients > 15 years old (OR 0.4, p-value < 0.001) and when the RDT was performed by a community health worker versus a laboratory technician (OR 0.4; p-value < 0.001). Health workers correctly prescribed anti-malarials for patients with positive RDT results, but ignored negative RDT results with 58% of patients with a negative RDT result treated with an anti-malarial., Conclusions: The results of this evaluation, combined with other published data and global recommendations, have been used to select RDTs for national scale-up. In addition, the study identified some key issues that need to be further delineated: the low field specificity of RDTs, variable RDT performance by different cadres of health workers and the need for a robust quality assurance system. Close monitoring of RDT scale-up will be needed to ensure that RDTs truly improve malaria case management.

The efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG vaccination and controls the multiplication of the vaccine. In these sensitized mice, BCG elicits only a transient immune response with a low frequency of mycobacterium-specific cells and no protective immunity against TB. In contrast, the efficacy of TB subunit vaccines was unaffected by prior exposure to environmental mycobacteria. Six different isolates from soil and sputum samples from Karonga district in Northern Malawi (a region in which BCG vaccination has no effect against pulmonary TB) were investigated in the mouse model, and two strains of the Mycobacterium avium complex were found to block BCG activity completely.

Non-tuberculous mycobacteria are free living saprophytic organisms commonly found in soil and water. Some are major causes of opportunistic infection, particularly in immuno-compromised patients, and may influence the efficacy of bacille Calmette-Guérin vaccinations. Many of these organisms are not amenable to culture, so information about their distribution is limited. PCR primers designed to amplify part of the mycobacterial 16S rRNA gene were applied to DNA extracted from cultured organisms and soil. The PCR products from soil contained sequences with similarity to slow growing mycobacteria similar to Mycobacterium lentiflavum, and to fast growing mycobacteria such as the xenobiotic degraders PYR-I and RJGII.

The minimum inhibitory concentrations (MICs) to the fluoroquinolones, ofloxacin (OFLX), ciprofloxacin (CPFX), sparfloxacin (SPFX), norfloxacin (NFLX), balofloxacin (BLFX) and CS-940, were determined in 100 clinical isolates of Mycobacterium tuberculosis. The MICs were determined with 1% egg-based Ogawa or agar-based Middlebrook 7H10 and each of them supplemented with oxidation-reduction color dye, 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC) by using the microculture technique. The MICs determined with Ogawa medium were approximately two- to four-fold higher when compared to those determined with Middlebrook agar medium. The supplement with STC slightly increased the MICs, probably as a result of easily recognizing small initial colonies. Among the six fluoroquinolones, CS-940 and SPFX showed the greatest antimycobacterial activities with inhibition of 50% of all the isolates at the concentrations between 0.25 to 0.5 microgram/ml. OFLX, CPFX and BLFX followed in potency at 0.5 to 2.0 micrograms /ml. NFLX was less potent requiring 8 to 16 micrograms/ml to inhibit 50% of the isolates.

In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival.

Objectives: To examine the relationship between maternal HIV infection, placental malaria infection, and infant mortality as a first step in investigating the possibility of increased vertical transmission of HIV due to placental malaria infection., Design: Retrospective analysis of data from a cohort study of mothers and infants in rural Malawi conducted from 1987 to 1990., Methods: Pregnant women in Malawi were enrolled in a study examining chemoprophylaxis during pregnancy. At delivery, placental malaria infection status was determined. Infants born into this study were visited every 2 months for the first 2-3 years of life. Deaths were investigated using a standardized 'verbal autopsy' interview. Maternal serum collected during pregnancy was tested for antibodies to HIV-1 by enzyme-linked immunosorbent assay with Western blot confirmation., Results: Overall, 138 (5.3%) of 2608 women in the study were HIV-1-seropositive. Infant mortality rates were 144 and 235 per 1000 live births for children born to HIV-seronegative and HIV-seropositive women, respectively (P < 0.001). In a multivariate model, the odds of dying during the post-neonatal period for an infant born to a mother with both placental malaria and HIV infection was 4.5 times greater than an infant born to a mother with only placental malaria, and between 2.7 and 7.7 times greater (depending on birthweight) than an infant born to a mother with only HIV infection., Conclusions: This study strongly suggests that exposure to both placental malaria infection and maternal HIV infection increases post-neonatal mortality beyond the independent risk associated with exposure to either maternal HIV or placental malaria infection. If confirmed, malaria chemoprophylaxis during pregnancy could decrease the impact of transmission of HIV from mother to infant.