Partnership Between a Federal Agency and 4 Tribal Nations to Improve COVID-19 Response Capacities.

Upon request from tribal nations, and as part of the Centers for Disease Control and Prevention's (CDC's) emergency response, CDC staff provided both remote and on-site assistance to tribes to plan, prepare, and respond to the COVID-19 pandemic. From April 2, 2020, through June 11, 2021, CDC deployed a total of 275 staff to assist 29 tribal nations. CDC staff typically collaborated in multiple work areas including epidemiology and surveillance (86%), contact tracing (76%), infection prevention control (72%), community mitigation (72%), health communication (66%), incident command structure (55%), emergency preparedness (38%), and worker safety (31%). We describe the activities of CDC staff in collaboration with 4 tribal nations, Northern Cheyenne, Hoopa Valley, Shoshone-Bannock, and Oglala Sioux Tribe, to combat COVID-19 and lessons learned from the engagement.

Disparities in Incidence of COVID-19 Among Underrepresented Racial/Ethnic Groups in Counties Identified as Hotspots During June 5-18, 2020 - 22 States, February-June 2020.

During January 1, 2020-August 10, 2020, an estimated 5 million cases of coronavirus disease 2019 (COVID-19) were reported in the United States.* Published state and national data indicate that persons of color might be more likely to become infected with SARS-CoV-2, the virus that causes COVID-19, experience more severe COVID-19-associated illness, including that requiring hospitalization, and have higher risk for death from COVID-19 (1-5). CDC examined county-level disparities in COVID-19 cases among underrepresented racial/ethnic groups in counties identified as hotspots, which are defined using algorithmic thresholds related to the number of new cases and the changes in incidence.† Disparities were defined as difference of ≥5% between the proportion of cases and the proportion of the population or a ratio ≥1.5 for the proportion of cases to the proportion of the population for underrepresented racial/ethnic groups in each county. During June 5-18, 205 counties in 33 states were identified as hotspots; among these counties, race was reported for ≥50% of cumulative cases in 79 (38.5%) counties in 22 states; 96.2% of these counties had disparities in COVID-19 cases in one or more underrepresented racial/ethnic groups. Hispanic/Latino (Hispanic) persons were the largest group by population size (3.5 million persons) living in hotspot counties where a disproportionate number of cases among that group was identified, followed by black/African American (black) persons (2 million), American Indian/Alaska Native (AI/AN) persons (61,000), Asian persons (36,000), and Native Hawaiian/other Pacific Islander (NHPI) persons (31,000). Examining county-level data disaggregated by race/ethnicity can help identify health disparities in COVID-19 cases and inform strategies for preventing and slowing SARS-CoV-2 transmission. More complete race/ethnicity data are needed to fully inform public health decision-making. Addressing the pandemic's disproportionate incidence of COVID-19 in communities of color can reduce the community-wide impact of COVID-19 and improve health outcomes.

Trends in Number and Distribution of COVID-19 Hotspot Counties - United States, March 8-July 15, 2020.

The geographic areas in the United States most affected by the coronavirus disease 2019 (COVID-19) pandemic have changed over time. On May 7, 2020, CDC, with other federal agencies, began identifying counties with increasing COVID-19 incidence (hotspots) to better understand transmission dynamics and offer targeted support to health departments in affected communities. Data for January 22-July 15, 2020, were analyzed retrospectively (January 22-May 6) and prospectively (May 7-July 15) to detect hotspot counties. No counties met hotspot criteria during January 22-March 7, 2020. During March 8-July 15, 2020, 818 counties met hotspot criteria for ≥1 day; these counties included 80% of the U.S. population. The daily number of counties meeting hotspot criteria peaked in early April, decreased and stabilized during mid-April-early June, then increased again during late June-early July. The percentage of counties in the South and West Census regions* meeting hotspot criteria increased from 10% and 13%, respectively, during March-April to 28% and 22%, respectively, during June-July. Identification of community transmission as a contributing factor increased over time, whereas identification of outbreaks in long-term care facilities, food processing facilities, correctional facilities, or other workplaces as contributing factors decreased. Identification of hotspot counties and understanding how they change over time can help prioritize and target implementation of U.S. public health response activities.

What Do We Know About Chagas Disease in the United States?

Chagas disease, caused by the parasite Trypanosoma cruzi, affects more than 5 million people worldwide leading to serious heart and gastrointestinal disease in a proportion of chronically infected patients. Important modes of transmission include vector-borne, congenital, and via blood transfusion or organ transplant from an infected donor. Vector-borne transmission of Chagas disease occurs in the Americas, including the southern half of North America, where the specific vector insects (triatomines), T. cruzi, and infected reservoir mammalian hosts are found. In the United States, there are estimated to be at least 300,000 cases of chronic Chagas disease among people originally from countries of Latin America where Chagas disease is endemic. Fewer than 30 cases of locally acquired infection have been documented in the United States, although a sylvatic transmission cycle has been known to exist in this country for at least a century. Studies defining risks for locally acquired infection and effective prevention strategies are needed to help prevent domestic transmission of T. cruzi To help address Chagas disease in the United States, improved health-care provider awareness and knowledge, better tools for screening and diagnosing patients, and wider availability of treatment drugs are needed.

Neglected parasitic infections in the United States: toxoplasmosis.

Toxoplasma gondii is a leading cause of severe foodborne illness in the United States. Population-based studies have found T. gondii infection to be more prevalent in racial/ethnic minority and socioeconomically disadvantaged groups. Soil contaminated with cat feces, undercooked meat, and congenital transmission are the principal sources of infection. Toxoplasmosis-associated illnesses include congenital neurologic and ocular disease; acquired illness in immunocompetent persons, most notably ocular disease; and encephalitis or disseminated disease in immunosuppressed persons. The association of T. gondii infection with risk for mental illness is intriguing and requires further research. Reduction of T. gondii in meat, improvements in hygiene and food preparation practices, and reduction of environmental contamination can prevent toxoplasmosis, but more research is needed on how to implement these measures. In addition, screening and treatment may help prevent toxoplasmosis or reduce the severity of disease in some settings.

Neglected parasitic infections in the United States: toxocariasis.

Toxocariasis is a preventable parasitic disease that is caused by the dog and cat roundworms Toxocara cani and T. cati, respectively. Humans become infected when they accidently ingest infectious Toxocara eggs commonly found in contaminated soil; children are most often affected. Clinical manifestations of Toxocara infection in humans include ocular toxocariasis and visceral toxocariasis. Although infection with Toxocara can cause devastating disease, the burden of toxocariasis in the United States population remains unknown. In addition, risk factors for acquiring infection need to be better defined, and research needs to be conducted to better understand the pathophysiology and clinical course of toxocariasis. Development of diagnostic tests would enable clinicians to detect active infection, and determination of optimal drug regiments would ensure patients were appropriately treated. Addressing these public health gaps is necessary to understand and address the impact of toxocariasis in the United States.

Using mitochondrial genome sequences to track the origin of imported Plasmodium vivax infections diagnosed in the United States.

Although the geographic origin of malaria cases imported into the United States can often be inferred from travel histories, these histories may be lacking or incomplete. We hypothesized that mitochondrial haplotypes could provide region-specific molecular barcodes for tracing the origin of imported Plasmodium vivax infections. An analysis of 348 mitochondrial genomes from worldwide parasites and new sequences from 69 imported malaria cases diagnosed across the United States allowed for a geographic assignment of most infections originating from the Americas, southeast Asia, east Asia, and Melanesia. However, mitochondrial lineages from Africa, south Asia, central Asia, and the Middle East, which altogether contribute the vast majority of imported malaria cases in the United States, were closely related to each other and could not be reliably assigned to their geographic origins. More mitochondrial genomes are required to characterize molecular barcodes of P. vivax from these regions.

Presumptive treatment and medical screening for parasites in refugees resettling to the United States.

More than 50,000 refugees are resettled to the United States annually, many from areas highly endemic for parasites. Some of these infections present little clinical consequence after migration, but others are responsible for morbidity and mortality. The Centers for Disease Control and Prevention has issued predeparture presumptive treatment and postarrival medical guidelines for the management of parasites. Although these guidelines are evidence based, there remain significant challenges to presumptive treatment programs in refugees. Gaps in the evidence continue; resettling populations are continually changing, thus altering the epidemiology; and there are logistical and cost barriers to fully implementing recommendations. This article will review the evolution and status of current guidelines, as well as identify gaps and challenges to full implementation. It is imperative for clinicians serving this population to be familiar with interventions received by refugees, since previous treatment will impact screening, diagnostic evaluation, and treatment decisions.

Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy.

BACKGROUND: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. METHODS: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. RESULTS: We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. CONCLUSIONS: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation.

Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis.

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability.

Associations between peripheral Plasmodium falciparum malaria parasitemia, human immunodeficiency virus, and concurrent helminthic infection among pregnant women in Malawi.

Approximately 2 billion persons worldwide are infected with schistosomiasis and soil-transmitted helminths (STH), many in areas where endemic malaria transmission coexists. Few data exist on associations between these infections. Nested within a larger clinical trial, primigravid and secundigravid women provided blood samples for human immunodeficiency virus (HIV) testing and peripheral malaria films and stool and urine for evaluation of STH and Schistosoma spp. during their initial antenatal clinic visit. The most common parasitic infections were malaria (37.6%), S. haematobium (32.3%), and hookworm (14.4%); 14.2% of women were HIV-infected. S. haematobium infection was associated with lower malarial parasite densities (344 versus 557 parasites/µL blood; P < 0.05). In multivariate analysis, HIV and hookworm infection were independently associated with malaria infection (adjusted odds ratio = 1.9 and 95% confidence interval = 1.2-3.0 for HIV; adjusted odds ratio = 1.9 and 95% confidence interval = 1.03-3.5 for hookworm). Concurrent helminthic infection had both positive and negative effects on malaria parasitemia among pregnant women in Malawi.

Plasma folate level and high-dose folate supplementation predict sulfadoxine-pyrimethamine treatment failure in pregnant women in Western kenya who have uncomplicated malaria.

UNLABELLED: Sulfadoxine-pyrimethamine (SP) inhibits folate metabolism by the malaria parasite. We investigated the association between folate levels and SP failure in pregnant women. Data from a trial to assess the effect that folate supplementation has on SP failure in 467 pregnant women were analyzed. Plasma folate levels were determined at enrollment and at day 7. High baseline folate levels, high parasite densities, and age <20 years were risk factors for SP failure. High-dose (5 mg daily) folate supplementation or high folate levels at day 7 were independent risk factors. Therefore, pregnant women receiving SP should receive low-/moderate-dose folate supplementation. TRIAL REGISTRATION: http://www.clinicaltrials.gov identifier: NCT00130065.

Malaria and anaemia among pregnant women at first antenatal clinic visit in Kisumu, western Kenya.

OBJECTIVE: To determine the prevalence of malaria and anaemia among urban and peri-urban women attending their first antenatal clinic (ANC) in an area of perennial malaria transmission. METHODS: Between November 2003 and May 2004 we screened first ANC attenders for malaria and anaemia in a large urban hospital in Kisumu (western Kenya) and interviewed them to obtain demographic and medical information. RESULTS: Among the 685 study participants, prevalence of malaria parasitaemia was 18.0%, prevalence of any anaemia (haemoglobin < 11 g/dl) was 69.1% and prevalence of moderate anaemia was (haemoglobin < 8 g/dl) 11.8%. Sixteen women were hospitalized during pregnancy, eight because of malaria. In multivariate analysis, young age, living in a house with mud walls, a visit to rural area, peri-urban residence, second trimester of pregnancy and Luo ethnicity were significant risk factors for malaria parasitaemia. Malaria was an important risk factor for any and moderate anaemia; use of an insecticide-treated net (ITN) was a protective factor for any anaemia. Married women with a higher level of education, better-quality housing and full-time employment were more likely to use an ITN. CONCLUSION: Malaria and anaemia are established problems by the time of the first ANC visit. Mechanisms to deliver ITNs to women of child-bearing age before they become pregnant need to be explored. Early ANC visits are warranted in order for women to benefit from policies aimed at reducing the burden of malaria and anaemia.

Pharmacokinetics of sulfadoxine-pyrimethamine in HIV-infected and uninfected pregnant women in Western Kenya.

BACKGROUND: Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV(+)) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV(-)) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP. METHODS: Seventeen pregnant HIV(-) women and 16 pregnant HIV(+) women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV(-) and 6 HIV(+) postpartum women returned 2-3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups. RESULTS: HIV status did not affect the area under the curve (AUC(0-->infinity)) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women, although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women, the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P<.001), and the median AUC(0-->infinity) was ~40% lower (22,816 vs 40,106 microg/mL/h, P<.001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics. CONCLUSION: Pregnancy significantly modifies the disposition of SP, whereas HIV status has little influence on pharmacokinetic parameters in pregnant women.

Safety and toxicity of sulfadoxine/pyrimethamine: implications for malaria prevention in pregnancy using intermittent preventive treatment.

Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering >or=2 treatment doses of sulfadoxine/pyrimethamine to pregnant women at predefined intervals after quickening (around 18-20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/pyrimethamine use in IPTp programmes in Africa, with 2-4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/pyrimethamine - when delivered as IPTp - has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.

Assessing malaria burden during pregnancy in Mali.

Malaria infection during pregnancy is associated with adverse consequences including low birth weight (LBW) and maternal anemia, particularly in primigravidae and secundigravidae. In preparation for a clinical trial of the efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) containing prevention regimens during pregnancy, we conducted a one-year cross sectional study in Koro and Bandiagara, Mali using an assessment methodology developed by the Centers for Disease Control and Prevention (CDC) to generate basic data on malarial burden during pregnancy. Two hundred and sixty-one and 192 women were enrolled in Koro and Bandiagara, respectively. Rates of placental parasitemia were 17.1 and 42.3% in Koro and Bandiagara, respectively, despite high (70-80%) use of preventive medication (mainly CQ). Low gravidity (1st and 2nd pregnancies) was associated with peripheral (p<0.001) and placental (p<0.001) malaria only in Bandiagara, whereas it was associated with low birth weight in both sites (p<0.001 in Koro and p=0.002 in Bandiagara). First and second pregnancies were the most important characteristics associated with placental malaria (RR=2.78, 95%CI 1.81-4.29) and (ARR=2.06, 95%CI 1.03-4.15) and low birth weight (RR=4.26, 95%CI 2.50-7.27) and (ARR=4.51, 95%CI 2.55-8.00). Birth during the rainy season was associated with placental infection in univariate analysis. Characteristics such as younger age, having fever during pregnancy, and unmarried status were associated with low birth weight only in univariate analysis and singleton premature delivery and low gravidity were associated with low birth weight in both univariate and multivariate analysis. Data from this assessment demonstrated the high burden of malaria during pregnancy in Mali. Results had been used by researchers as local reference data and by ministry of health for to stop recommending CQ prophylaxis. The methodology could be used by other malaria-endemic countries to direct their national malaria program efforts.

Treatment of malaria in the United States: a systematic review.

CONTEXT: Many US clinicians and laboratory personnel are unfamiliar with the diagnosis and treatment of malaria. OBJECTIVES: To examine the evidence base for management of uncomplicated and severe malaria and to provide clinicians with practical recommendations for the diagnosis and treatment of malaria in the United States. EVIDENCE ACQUISITION: Systematic MEDLINE search from 1966 to 2006 using the search term malaria (with the subheadings congenital, diagnosis, drug therapy, epidemiology, and therapy). Additional references were obtained from searching the bibliographies of pertinent articles and by reviewing articles suggested by experts in the treatment of malaria in North America. EVIDENCE SYNTHESIS: Important measures to reduce morbidity and mortality from malaria in the United States include the following: obtaining a travel history, considering malaria in the differential diagnosis of fever based on the travel history, and prompt and accurate diagnosis and treatment. Chloroquine remains the treatment of choice for Plasmodium falciparum acquired in areas without chloroquine-resistant strains. In areas with chloroquine resistance, a combination of atovaquone and proguanil or quinine plus tetracycline or doxycycline or clindamycin are the best treatment options. Chloroquine remains the treatment of choice for all other malaria species, with the exception of P vivax acquired in Indonesia or Papua New Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine plus tetracycline or doxycycline as alternatives. Quinidine is currently the recommended treatment for severe malaria in the United States because the artemisinins are not yet available. Severe malaria occurs when a patient with asexual malaria parasitemia, and no other confirmed cause of symptoms, has 1 or more designated clinical or laboratory findings. The only adjunctive measure recommended in severe malaria is exchange transfusion. CONCLUSIONS: Malaria remains a diagnostic and treatment challenge for US clinicians as increasing numbers of persons travel to and emigrate from malarious areas. A strong evidence base exists to help clinicians rapidly initiate appropriate therapy and minimize the major mortality and morbidity burdens caused by this disease.

Atovaquone-proguanil: report from the CDC expert meeting on malaria chemoprophylaxis (II).

The fixed dose combination of atovaquone and proguanil hydrochloride, marketed under the trade name Malarone, is the most recently approved agent in North America for the prevention and treatment of chloroquine- and multi-drug resistant Plasmodium falciparum malaria. In both adult and pediatric populations, atovaquone-proguanil demonstrates consistently high protective efficacy against P. falciparum, and in treatment trials, cure rates exceed 93%. Only a handful of genetically confirmed treatment failures have been reported to date. Atovaquone-proguanil has an excellent safety profile during both prophylaxis and treatment courses, with severe adverse events rarely reported. This topical review will examine the evidence behind the current indications for use of atovaquone-proguanil, and will summarize the current body of literature surrounding safety and tolerability.