COVID-19 Epidemiology during Delta Variant Dominance Period in 45 High-Income Countries, 2020-2021.

The SARS-CoV-2 Delta variant, first identified in October 2020, quickly became the dominant variant worldwide. We used publicly available data to explore the relationship between illness and death (peak case rates, death rates, case-fatality rates) and selected predictors (percentage vaccinated, percentage of the population >65 years, population density, testing volume, index of mitigation policies) in 45 high-income countries during the Delta wave using rank-order correlation and ordinal regression. During the Delta-dominant period, most countries reported higher peak case rates (57%) and lower peak case-fatality rates (98%). Higher vaccination coverage was protective against peak case rates (odds ratio 0.95, 95% CI 0.91-0.99) and against peak death rates (odds ratio 0.96, 95% CI 0.91-0.99). Vaccination coverage was vital to preventing infection and death from COVID-19 during the Delta wave. As new variants emerge, public health authorities should encourage the uptake of COVID-19 vaccination and boosters.

Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America.

INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

Pregnant women and infants as sentinel populations to monitor prevalence of malaria: results of pilot study in Lake Zone of Tanzania.

BACKGROUND: As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9-12 months of age for measles vaccination. METHODS: Pregnant women attending first ANC and infants nine to 12 months old presenting for measles vaccination at a non-probability sample of 54 HFs in Tanzania's Lake Zone (Mara, Mwanza and Kagera Regions) were screened for malaria infection using a malaria rapid diagnostic test (RDT) from December 2012 to November 2013, regardless of symptoms. Participants who tested positive were treated for malaria per national guidelines. Data were collected monthly. RESULTS: Overall 89.9 and 78.1 % of expected monthly reports on malaria infection prevalence were received for pregnant women and infants, respectively. Among 51,467 pregnant women and 35,155 infants attending routine preventive HF visits, 41.2 and 37.3 % were tested with RDT, respectively. Malaria infection prevalence was 12.8 % [95 % confidence interval (CI) 11.3-14.3] among pregnant women and 11.0 % (95 % CI 9.5-12.5) among infants, and varied by month. There was good correlation of the prevalence of malaria among pregnant women and infants at the HF level (Spearman rho = 0.6; p < 0.001). This approach is estimated to cost $1.28 for every person tested, with the RDT accounting for 72 % of the cost. CONCLUSIONS: Malaria infection was common and well correlated among pregnant women and infants attending routine health services. Routine screening of these readily accessible populations may offer a practical strategy for continuously tracking malaria trends, particularly seasonal variation. Positivity rates among afebrile individuals presenting for routine care offer an advantage as they are unaffected by the prevalence of other causes of febrile illness, which could influence positivity rates among febrile patients presenting to outpatient clinics. The data presented here suggest that in addition to contributing to clinical management, ongoing screening of pregnant women could be used for routine surveillance and detection of hotspots.

Quality assurance of malaria rapid diagnostic tests used for routine patient care in rural Tanzania: microscopy versus real-time polymerase chain reaction.

BACKGROUND: The World Health Organization (WHO) recommends parasitologic confirmation of suspected malaria cases before treatment. Due to the limited availability of quality microscopy services, this recommendation has become scalable following increased use of antigen-detecting malaria rapid diagnostic tests (RDTs) in many malaria-endemic countries. This study was carried out to monitor quality of RDT performance in selected health facilities using two quality assurance (QA) methods: reference microscopy and detection of parasite DNA by real-time quantitative polymerase chain reaction (qPCR) on dried blood spots (DBS). METHODS: Blood samples for QA were collected from patients undergoing RDT for diagnostic confirmation of malaria during two to three consecutive days per month in 12 health facilities in rural Tanzania. Stained blood smears (BS) were first examined at the district hospitals (BS1) and then at a reference laboratory (BS2). Discordant BS1 and BS2 results prompted a third examination. Molecular analysis was carried out at the Ifakara Health Institute laboratory in Bagamoyo. RESULTS: Malaria RDTs had a higher positivity rate (6.5%) than qPCR (4.2%) or microscopy (2.9% for BS1 and 2.5% for BS2). Poor correlation was observed between RDT and BS results: BS1 (K = 0.5), BS2 (K = 0.43) and qPCR (K = 0.45), challenging the utility of these tests for RDT QA. In addition, many challenges related to qPCR processing were recorded and long delays in obtaining QA test results for both microscopy and qPCR. CONCLUSIONS: Overall there was limited agreement among the three diagnostic approaches and neither microscopy nor qPCR appear to be good QA options for RDTs under field conditions.

Design, implementation and evaluation of a national campaign to deliver 18 million free long-lasting insecticidal nets to uncovered sleeping spaces in Tanzania.

BACKGROUND: Since 2004, the Tanzanian National Voucher Scheme has increased availability and accessibility of insecticide-treated nets (ITNs) to pregnant women and infants by subsidizing the cost of nets purchased. From 2008 to 2010, a mass distribution campaign delivered nine million long-lasting insecticidal nets (LLINs) free-of-charge to children under-five years of age in Tanzania mainland. In 2010 and 2011, a Universal Coverage Campaign (UCC) led by the Ministry of Health and Social Welfare (MoHSW) was implemented to cover all sleeping spaces not yet reached through previous initiatives. METHODS: The UCC was coordinated through a unit within the National Malaria Control Programme. Partners were contracted by the MoHSW to implement different activities in collaboration with local government authorities. Volunteers registered the number of uncovered sleeping spaces in every household in the country. On this basis, LLINs were ordered and delivered to village level, where they were issued over a three-day period in each zone (three regions). Household surveys were conducted in seven districts immediately after the campaign to assess net ownership and use. RESULTS: The UCC was chiefly financed by the Global Fund to Fight AIDS, Tuberculosis and Malaria with important contributions from the US President's Malaria Initiative. A total of 18.2 million LLINs were delivered at an average cost of USD 5.30 per LLIN. Overall, 83% of the expenses were used for LLIN procurement and delivery and 17% for campaign associated activities. Preliminary results of the latest Tanzania HIV Malaria Indicator Survey (2011-12) show that household ownership of at least one ITN increased to 91.5%. ITN use, among children under-five years of age, improved to 72.7% after the campaign. ITN ownership and use data post-campaign indicated high equity across wealth quintiles. CONCLUSION: Close collaboration among the MoHSW, donors, contracted partners, local government authorities and volunteers made it possible to carry out one of the largest LLIN distribution campaigns conducted in Africa to date. Through the strong increase of ITN use, the recent activities of the national ITN programme will likely result in further decline in child mortality rates in Tanzania, helping to achieve Millennium Development Goals 4 and 6.

Routine Healthcare Facility- and Antenatal Care-Based Malaria Surveillance: Challenges and Opportunities.

Most monitoring and evaluation tools for measuring malaria burden, intervention coverage, and impact of interventions use periodic nationally representative cross-sectional household surveys. These provide advantages in terms of selecting a large, unbiased, population-based sample; however, they are infrequently conducted, are resource-intensive, and do not provide longitudinal data with sufficient granularity. Given the heterogeneity of malaria transmission within most endemic countries, systems with the capacity to provide more granular and frequent data would be more actionable by national malaria control programs and local implementing partners. There is increasing interest in using routine health facility data, usually from outpatient department visits, for monitoring malaria burden. Data from pregnant women attending antenatal care (ANC) could minimize bias related to fever care-seeking among outpatient department visits and provide more granular parasite prevalence data. Most pregnant women attend ANC at least once and are thus highly representative of the overall pregnant population. A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged < 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time. Additional data are needed to assess whether pregnant women are sufficiently representative of the overall population to yield valid malaria prevalence and intervention coverage estimates. Although use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable.

Design, implementation and evaluation of a national campaign to distribute nine million free LLINs to children under five years of age in Tanzania.

BACKGROUND: After a national voucher scheme in 2004 provided pregnant women and infants with highly subsidized insecticide-treated nets (ITNs), use among children under five years (U5s) in mainland Tanzania increased from 16% in 2004 to 26.2% in 2007. In 2008, the Ministry of Health and Social Welfare planned a catch-up campaign to rapidly and equitably deliver a free long-lasting insecticidal net (LLIN) to every child under five years in Tanzania. METHODS: The ITN Cell, a unit within the National Malaria Control Programme (NMCP), coordinated the campaign on behalf of the Ministry of Health and Social Welfare. Government contractors trained and facilitated local government officials to supervise village-level volunteers on a registration of all U5s and the distribution and issuing of LLINs. The registration results formed the basis for the LLIN order and delivery to village level. Caregivers brought their registration coupons to village issuing posts during a three-day period where they received LLINs for their U5s. Household surveys in five districts assessed ITN ownership and use immediately after the campaign. RESULTS: Nine donors contributed to the national campaign that purchased and distributed 9.0 million LLINs at an average cost of $7.07 per LLIN, including all campaign-associated activities. The campaign covered all eight zones of mainland Tanzania, the first region being covered separately during an integrated measles immunization/malaria LLIN distribution in August 2008, and was implemented one zone at a time from March 2009 until May 2010. ITN ownership at household level increased from Tanzania's 2008 national average of 45.7% to 63.4%, with significant regional variations. ITN use among U5s increased from 28.8% to 64.1%, a 2.2-fold increase, with increases ranging from 22.1-38.3% percentage points in different regions. CONCLUSION: A national-level LLIN distribution strategy that fully engaged local government authorities helped avoid additional burden on the healthcare system. Distribution costs per net were comparable to other public health interventions. Particularly among rural residents, ITN ownership and use increased significantly for the intended beneficiaries. The upcoming universal LLIN distribution and further behaviour change communication will further improve ITN ownership and use in 2010-2011.

Malaria and Parasitic Neglected Tropical Diseases: Potential Syndemics with COVID-19?

The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections are likely. Both malaria and parasitic NTDs can alter immunologic responses to other infectious agents. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with malaria parasites and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age-groups. Enhancing surveillance platforms could provide signals that indicate whether malaria, NTDs, and COVID-19 are syndemics (synergistic epidemics). Based on the prevalence of malaria and NTDs in specific localities, efforts to characterize COVID-19 in LMICs could be expanded by adding testing for malaria and NTDs. Such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of COVID-19 in LMICs and potentially helping to mitigate its impact.

Clearance dynamics of lactate dehydrogenase and aldolase following antimalarial treatment for Plasmodium falciparum infection.

BACKGROUND: Lingering post-treatment parasite antigen in blood complicates malaria diagnosis through antigen detection. Characterization of antigen clearance dynamics is important for interpretation of positive antigen detection tests. RESULTS: We used a bead-based serological assay to measure lactate dehydrogenase (LDH), aldolase (Aldo), and histidine-rich protein 2 (HRP2) levels in 196 children with Plasmodium falciparum malaria treated with effective antimalarials and followed for 28 to 42 days as part of therapeutic efficacy studies in Angola. Compared to pre-treatment levels, antigen concentrations two days after treatment declined by 99.7% for LDH, 96.3% for Aldo, and 54.6% for HRP2. After Day 2, assuming a first-order kinetics clearance model, half-lives of the antigens were 1.8 days (95% CI: 1.5-2.3) for LDH, 3.2 days (95% CI: 3.0-3.4) for Aldo, and 4.8 days (95% CI: 4.7-4.9) for HRP2. CONCLUSIONS: LDH and Aldo show substantially different clearance rates than HRP2, and their presence is largely indicative of active infection.

Markets, voucher subsidies and free nets combine to achieve high bed net coverage in rural Tanzania.

BACKGROUND: Tanzania has a well-developed network of commercial ITN retailers. In 2004, the government introduced a voucher subsidy for pregnant women and, in mid 2005, helped distribute free nets to under-fives in small number of districts, including Rufiji on the southern coast, during a child health campaign. Contributions of these multiple insecticide-treated net delivery strategies existing at the same time and place to coverage in a poor rural community were assessed. METHODS: Cross-sectional household survey in 6,331 members of randomly selected 1,752 households of 31 rural villages of Demographic Surveillance System in Rufiji district, Southern Tanzania was conducted in 2006. A questionnaire was administered to every consenting respondent about net use, treatment status and delivery mechanism. FINDINGS: Net use was 62.7% overall, 87.2% amongst infants (0 to 1 year), 81.8% amongst young children (>1 to 5 years), 54.5% amongst older children (6 to 15 years) and 59.6% amongst adults (>15 years). 30.2% of all nets had been treated six months prior to interview. The biggest source of nets used by infants was purchase from the private sector with a voucher subsidy (41.8%). Half of nets used by young children (50.0%) and over a third of those used by older children (37.2%) were obtained free of charge through the vaccination campaign. The largest source of nets amongst the population overall was commercial purchase (45.1% use) and was the primary means for protecting adults (60.2% use). All delivery mechanisms, especially sale of nets at full market price, under-served the poorest but no difference in equity was observed between voucher-subsidized and freely distributed nets. CONCLUSION: All three delivery strategies enabled a poor rural community to achieve net coverage high enough to yield both personal and community level protection for the entire population. Each of them reached their relevant target group and free nets only temporarily suppressed the net market, illustrating that in this setting that these are complementary rather than mutually exclusive approaches.

Transmission network analysis to complement routine tuberculosis contact investigations.

OBJECTIVE: We examined the feasibility and value of network analysis to complement routine tuberculosis (TB) contact investigation procedures during an outbreak. METHODS: We reviewed hospital, health department, and jail records and interviewed TB patients. Mycobacterium tuberculosis isolates were genotyped. We evaluated contacts of TB patients for latent TB infection (LTBI) and TB, and analyzed routine contact investigation data, including tuberculin skin test (TST) results. Outcomes included number of contacts identified, number of contacts evaluated, and their TST status. We used network analysis visualizations and metrics (reach, degree, betweenness) to characterize the outbreak. RESULTS: secondary TB patients and more than 1200 contacts. Genotyping detected a 21-band pattern of a strain W variant. No HIV-infected patients were diagnosed. Contacts prioritized by network analysis were more likely to have LTBI than nonprioritized contacts (odds ratio=7.8; 95% confidence interval=1.6, 36.6). Network visualizations and metrics highlighted patients central to sustaining the outbreak and helped prioritize contacts for evaluation. CONCLUSIONS: A network-informed approach to TB contact investigations provided a novel means to examine large quantities of data and helped focus TB control.

Implementing Impact Evaluations of Malaria Control Interventions: Process, Lessons Learned, and Recommendations.

As funding for malaria control increased considerably over the past 10 years resulting in the expanded coverage of malaria control interventions, so did the need to measure the impact of these investments on malaria morbidity and mortality. Members of the Roll Back Malaria (RBM) Partnership undertook impact evaluations of malaria control programs at a time when there was little guidance in terms of the process for conducting an impact evaluation of a national-level malaria control program. The President's Malaria Initiative (PMI), as a member of the RBM Partnership, has provided financial and technical support for impact evaluations in 13 countries to date. On the basis of these experiences, PMI and its partners have developed a streamlined process for conducting the evaluations with a set of lessons learned and recommendations. Chief among these are: to ensure country ownership and involvement in the evaluations; to engage stakeholders throughout the process; to coordinate evaluations among interested partners to avoid duplication of efforts; to tailor the evaluation to the particular country context; to develop a standard methodology for the evaluations and a streamlined process for completion within a reasonable time; and to develop tailored dissemination products on the evaluation for a broad range of stakeholders. These key lessons learned and resulting recommendations will guide future impact evaluations of malaria control programs and other health programs.

Severe or fatal liver injury in 50 patients in the United States taking rifampin and pyrazinamide for latent tuberculosis infection.

BACKGROUND: Severe liver injuries were attributed to the rifampin and pyrazinamide (RZ) regimen after it was recommended for treating latent tuberculosis infection. Implicating RZ as the likeliest cause required excluding alternative causes. METHODS: US health departments reported data on patients who died or were hospitalized for liver disease within 1 month after taking RZ for latent tuberculosis infection from October 1998 through March 2004. The circumstances were investigated on site for each case. Illness characteristics, reasons for RZ treatment, doses and frequency of administration of pyrazinamide, monitoring during treatment, and causes of liver injury were determined. RESULTS: Liver injury was attributable to RZ use for all 50 patients reported, 12 of whom died. For 47 patients, RZ was the likeliest cause of liver injury. The median patient age was 44 years (range, 17-73 years). Thirty-two patients (64%) were male. Seven (16%) of 43 patients tested had hepatitis C virus antibodies, 1 (2%) of 45 had chronic hepatitis B, 3 (14%) of 22 had positive results of HIV serologic tests, 34 (71%) of 48 had alcohol use noted, and 33 (66%) of 50 were taking additional hepatotoxic medications. Six patients, 2 of whom died, had no predictors for liver disease. Patients who died were older (median age, 52 vs. 42 years; P=.08) and took a greater number of other medications (median number of medications, 4 vs. 2; P=.05) than did those who recovered, but these 2 factors were correlated (P<.01). Thirty-one patients (62%) were monitored according to guidelines, 9 of whom died. CONCLUSIONS: RZ was the likeliest cause of most of these liver injuries, some of which were fatal in spite of monitoring. Fatality was predicted by age or use of other medications, but none of the cofactors showed promise as a reliable clinical predictor of severe liver injury.

National survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection.

BACKGROUND: Cases of severe and fatal liver injury were reported after a 2-month course of rifampin-pyrazinamide therapy was recommended in 2000 as an alternative to isoniazid for treatment of latent tuberculosis infection. We estimated rates of rifampin-pyrazinamide-associated liver injury and compared these with historical rates for isoniazid. METHODS: We conducted a survey of state and city tuberculosis programs and other health care settings in the United States where rifampin-pyrazinamide was prescribed. The number of rifampin-pyrazinamide therapy initiations was collected, as well as the number of occurrences of (1) asymptomatic aspartate aminotransferase serum concentration >5 times the upper limit of normal, (2) symptomatic hepatitis (in which the patient was not hospitalized), (3) hospitalization for liver injury, (4) death with liver injury, and (5) treatment completion. We also searched a national pharmacy claims database (Verispan). Rates of these events were calculated. RESULTS: Among 139 programs, 110 (79%) responded; 87 (79%) had initiated rifampin-pyrazinamide therapy for a total of 8087 patients between January 2000 and June 2002. Rates per 1000 rifampin-pyrazinamide therapy initiations during this period were 25.6 (95% confidence interval [CI], 22.3-29.3) for asymptomatic aspartate aminotransferase level >5 times the upper limit of normal and 18.7 (95% CI, 15.9-21.9) for hepatitis. Seven fatalities and 23 hospitalizations occurred, with rates of 0.9 (95% CI, 0.4-1.9) and 2.8 (95% CI, 1.8-4.3) per 1000 rifampin-pyrazinamide therapy initiations, respectively. Of 8087 patients, 64% completed rifampin-pyrazinamide therapy. The Verispan search revealed 1 rifampin-pyrazinamide-associated hospitalization (2.9 hospitalizations per 1000 rifampin-pyrazinamide therapy initiations; 95% CI, 0.1-18.4) and no deaths. Articles on the use of isoniazid therapy for latent tuberculosis infection that were published after 1990 reported fatality rates of 0.0-0.3 deaths per 1000 persons. CONCLUSIONS: Rates of liver injury, hospitalization, and death associated with rifampin-pyrazinamide therapy exceed rates reported for isoniazid therapy. Because earlier randomized trials of rifampin-pyrazinamide lacked adequate statistical power to detect fatal events, the Centers for Disease Control and Prevention recommends that rifampin-pyrazinamide generally should not be used for treatment of latent tuberculosis infection.

Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999-2010.

BACKGROUND: Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period. METHODS: Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6-59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM. RESULTS: Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7-65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6-28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6-59 months declined 50% between 2005 (11.1%; 95% CI, 10.0-12.3%) and 2010 (5.5%; 95% CI, 4.7-6.4%) and U5CM declined by 45% between baseline (1995-9) and endpoint (2005-9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1-23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains. CONCLUSION: Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1-24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival.

Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities.

BACKGROUND: The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management. METHODS: We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. FINDINGS: We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65-83) and 35 of 73 were actively treating malaria cases (48%, 36-60) compared with 106 of 112 (95%, 89-98) and 102 of 106 (96%, 91-99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000-77 000) fewer malaria cases seen at health facilities in 2014. INTERPRETATION: The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response. FUNDING: Global Fund to Fight AIDS, Tuberculosis and Malaria, and President's Malaria Initiative.

Outbreak of tuberculosis among homeless persons coinfected with human immunodeficiency virus.

We investigated a cluster of patients with tuberculosis (TB) in North Carolina and determined the extent of transmission of 1 strain of Mycobacterium tuberculosis. A retrospective cohort study was conducted. Homeless shelter attendance and medical records for 1999 and 2000 were reviewed. The period of exposure to M. tuberculosis was determined, and shelter residents were offered TB screening. DNA fingerprinting was performed on 72 M. tuberculosis isolates. In addition to the initial index cluster of 9 patients, another 16 patients were identified. Isolates of M. tuberculosis from all 25 patients shared a matching DNA fingerprint pattern. All but 1 patient was male, 22 (88%) were African American, and 14 (56%) were human immunodeficiency virus-infected. An epidemiological link to a single shelter was identified for all but 1 patient. Earlier recognition of this shelter as a site of M. tuberculosis transmission could have been facilitated through innovative approaches to contact investigation and through genetic typing of isolates.

Placental malaria is rare among Zanzibari pregnant women who did not receive intermittent preventive treatment in pregnancy.

Zanzibar has transitioned from malaria control to the pre-elimination phase, and the continued need for intermittent preventive treatment during pregnancy (IPTp) has been questioned. We conducted a prospective observational study to estimate placental malaria positivity rate among women who did not receive IPTp with sulfadoxine-pyrimethamine. A convenience sample of pregnant women was enrolled from six clinics on the day of delivery from August of 2011 to September of 2012. Dried placental blood spot specimens were analyzed by polymerase chain reaction (PCR); 9 of 1,349 specimens (0.7%; precision estimate = 0.2-1.1%) were PCR-positive for Plasmodium falciparum. Placental infection was detected on both Pemba (N = 3) and Unguja (N = 6). Placental malaria positivity in Zanzibar was low, even in the absence of IPTp. It may be reasonable for the Ministry of Health to consider discontinuing IPTp, intensifying surveillance efforts, and promoting insecticide-treated nets and effective case management of malaria in pregnancy.

Health workers' use of malaria rapid diagnostic tests (RDTs) to guide clinical decision making in rural dispensaries, Tanzania.

Rapid diagnostic tests (RDTs) were developed as an alternative to microscopy for malaria diagnosis. The RDTs detect malaria parasite antigen(s) in whole blood with high sensitivity and specificity. We assessed health worker malaria treatment practices after the introduction of RDTs in peripheral health facilities without microscopy. From December 2007 to October 2008, we introduced histidine-rich protein II (HRP-2)-based ParaHIT RDTs for routine use in 12 health facilities in Rufiji District, Tanzania. Health workers received training on how to perform RDTs for patients 5 years of age or older with fever or suspected malaria. Children < 5 years of age were to be treated empirically per national guidelines. Among the 30,195 patients seen at these 12 health facilities, 10,737 (35.6%) were tested with an RDT for malaria. 88.3% (9,405/10,648) of tested patients reported fever or history of fever and 2.7% (289/10,677) of all tested individuals were children < 5 years of age. The RDT results were recorded for 10,650 patients (99.2%). Among the 5,488 (51.5%) RDT-positive patients, 5,256 (98.6%) were treated with an appropriate first-line antimalarial per national guidelines (artemether-lumefantrine or quinine). Among the 5,162 RDT-negative patients, only 205 (4.0%) were treated with an antimalarial. Other reported treatments included antibiotics and antipyretics. Implementation of RDTs in rural health facilities resulted in high adherence to national treatment guidelines. Patients testing negative by RDT were rarely treated with antimalarials. Unapproved antimalarials were seldom used. Health workers continued to follow guidelines for the empiric treatment of febrile children.