Anatomical Site, Viral Ribonucleic Acid Abundance, and Time of Sampling Correlate With Molecular Detection of Severe Acute Respiratory Syndrome Coronavirus 2 During Infection.

BACKGROUND: Nasopharyngeal (NP) swabs are the standard for SARS-CoV-2 diagnosis. If less invasive alternatives to NP swabs (eg, oropharyngeal [OP] or nasal swabs [NS]) are comparably sensitive, the use of these techniques may be preferable in terms of comfort, convenience, and safety. METHODS: This study compared the detection of SARS-CoV-2 in swab samples collected on the same day among participants with at least one positive PCR test. RESULTS: Overall, 755 participants had at least one set of paired swabs. Concordance between NP and other swab types was 75% (NS), 72% (OP), 54% (rectal swabs [RS]), and 78% (NS/OP combined). Kappa values were moderate for the NS, OP, and NS/OP comparisons (0.50, 0.45, and 0.54, respectively). Highest sensitivity relative to NP (0.87) was observed with a combination of NS/OP tests (positive if either NS or OP was positive). Sensitivity of the non-NP swab types was highest in the first week postsymptom onset and decreased thereafter. Similarly, virus RNA quantity was highest in the NP swabs as compared with NS, OP, and RS within two weeks postsymptom onset. OP and NS performance decreased as virus RNA quantity decreased. No differences were noted between NS specimens collected at home or in clinic. CONCLUSIONS: NP swabs detected more SARS-CoV-2 cases than non-NP swabs, and the sensitivity of the non-NP swabs decreased with time postsymptom onset. While other swabs may be simpler to collect, NP swabs present the best chance of detecting SARS-CoV-2 RNA, which is essential for clinical care as well as genomic surveillance.

Performance of the inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus) Instrument in Patients With Coronavirus Disease 2019.

BACKGROUND: The inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus) is a patient-reported outcome data collection instrument assessing symptoms of viral respiratory tract infections across 8 body systems. This study evaluated the measurement properties of FLU-PRO Plus in a study enrolling individuals with coronavirus disease 2019 (COVID-19). METHODS: Data from a prospective cohort study (EPICC) in US Military Health System beneficiaries evaluated for COVID-19 was utilized. Adults with symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with FLU-PRO Plus survey information within 1 week of symptom onset were included. Reliability of FLU-PRO Plus was estimated using intraclass correlation coefficient (ICC; 2 days' reproducibility). Known-groups validity was assessed using patient global assessment (PGA) of disease severity. Patient report of return to usual health was used to assess responsiveness (day 1-6/7). RESULTS: Two hundred twenty-six SARS-CoV-2-positive participants were included in the analysis. Reliability among those who reported no change in their symptoms from one day to the next was high for most domains (ICC range, 0.68-0.94 for day 1 to day 2). Construct validity was demonstrated by moderate to high correlation between the PGA rating of disease severity and domain and total scores (eg, total scores correlation: 0.69 [influenza-like illness severity], 0.69 [interference in daily activities], and -0.58 [physical health]). In addition, FLU-PRO Plus demonstrated good known-groups validity, with increasing domain and total scores observed with increasing severity ratings. CONCLUSIONS: FLU-PRO Plus performs well in measuring signs and symptoms in SARS-CoV-2 infection with excellent construct validity, known-groups validity, and responsiveness to change. Standardized data collection instruments facilitate meta-analyses, vaccine effectiveness studies, and other COVID-19 research activities.

COVID-19 Outcomes Among US Military Health System Beneficiaries Include Complications Across Multiple Organ Systems and Substantial Functional Impairment.

BACKGROUND: We evaluated clinical outcomes, functional burden, and complications 1 month after coronavirus disease 2019 (COVID-19) infection in a prospective US Military Health System (MHS) cohort of active duty, retiree, and dependent populations using serial patient-reported outcome surveys and electronic medical record (EMR) review. METHODS: MHS beneficiaries presenting at 9 sites across the United States with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, a COVID-19-like illness, or a high-risk SARS-CoV-2 exposure were eligible for enrollment. Medical history and clinical outcomes were collected through structured interviews and International Classification of Diseases-based EMR review. Risk factors associated with hospitalization were determined by multivariate logistic regression. RESULTS: A total of 1202 participants were enrolled. There were 1070 laboratory-confirmed SARS-CoV-2 cases and 132 SARS-CoV-2-negative participants. In the first month post-symptom onset among the SARS-CoV-2-positive cases, there were 212 hospitalizations, 80% requiring oxygen, 20 ICU admissions, and 10 deaths. Risk factors for COVID-19-associated hospitalization included race (increased for Asian, Black, and Hispanic compared with non-Hispanic White), age (age 45-64 and 65+ compared with <45), and obesity (BMI≥30 compared with BMI<30). Over 2% of survey respondents reported the need for supplemental oxygen, and 31% had not returned to normal daily activities at 1 month post-symptom onset. CONCLUSIONS: Older age, reporting Asian, Black, or Hispanic race/ethnicity, and obesity are associated with SARS-CoV-2 hospitalization. A proportion of acute SARS-CoV-2 infections require long-term oxygen therapy; the impact of SARS-CoV-2 infection on short-term functional status was substantial. A significant number of MHS beneficiaries had not yet returned to normal activities by 1 month.

Travel-Related Risk Behaviors and Antibiotic Use Among Older Travelers.

BACKGROUND: Antibiotic stewardship in the pretravel care of older adults is important to effectively treat infections while minimizing harm from side effects and unnecessary antibiotic use. The objective of this study was to compare the characteristics, risk behaviors, infectious diseases, and antibiotic use between older (≥60 years) and younger (18-59 years) travelers. METHODS: TravMil is a prospective, observational cohort of United States (US) Department of Defense beneficiaries traveling outside the continental US for ≤6.5 months. For this analysis, we included adults enrolled pretravel between January 2010 and August 2018 and excluded active duty personnel on deployment. Pre and post-travel surveys captured trip characteristics, exposures, illnesses, and antibiotic use. RESULTS: A total of 1742 travelers were analyzed: 747 (42.9%) were aged ≥60 years and 995 (57.1%) were aged 18-59 years. Older travelers were less likely to engage in high-risk dietary behaviors and experience travelers' diarrhea than younger travelers (18.2% vs 22.9%; P < .05). Influenza-like illness (12.5%) and febrile illness (3.4%) occurred less frequently in the older cohort. Antibiotic use for self-treatment was common in both age groups (25.7% vs 26.7%) and often inappropriate, for example, for treatment of occasional loose stool or mild travelers' diarrhea (67.0% [67/100] in older adults vs 57.6% [83/144] in younger adults; P < .05), and influenza-like illness (63.4% [64/101] vs 58.6% [68/116], respectively; P < .05). CONCLUSIONS: Older travelers were less likely to engage in high-risk behaviors and experience travelers' diarrhea, and both age groups experienced mild, self-limited infections. Inappropriate use of antibiotics was common, suggesting that antimicrobial stewardship should be emphasized at pretravel counseling with international travelers.

Prospective Evaluation of an Abbreviated Test Battery to Screen for Neurocognitive Impairment in HIV-Positive Military Members.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects around 20-50% of people living with HIV (PLWH). Although batteries of tests are used to identify neurocognitive impairment (NCI), they are long and difficult to perform during a routine clinic visit, thus impairing the ability to diagnose HAND. Therefore, a brief yet sensitive screening tool to identify NCI is necessary. This study prospectively evaluated an abbreviated screening battery with reported 86.5%/87.1% sensitivity/specificity, identified from a planned post-hoc analysis in a prior neurocognitive study among military PLWH. Adult HIV-positive military beneficiaries in the U.S. Military HIV Natural History Study, who agreed to undergo a comprehensive seven-domain neuropsychological battery (16 tests), and who completed an additional 20-min abbreviated battery (AB), comprised of four tests, prior to the full battery (FB) were included in this analysis. A group of 169 individuals completed both tests, of which 25.4% had a positive AB and 17.8% had NCI on FB (global deficit score ≥ 0.5). With the FB as the reference standard, the specificity for the AB was 79.9% (73.2-86.5), however the sensitivity was 50.0% (32.1-67.9). In those with NCI by FB but not AB, the most common impaired domains were executive function (73.3%) and memory (73.3%), both being domains not fully tested by the AB. An abbreviated HAND screening battery of four tests requiring approximately 20 min provided a relatively high level of specificity but lacked sensitivity for detection of NCI. Inclusion of additional domains or alternative scoring approaches may improve sensitivity but require further study. Continued efforts are needed to develop an effective brief screening test for HAND.

Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era.

BACKGROUND: As morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era. METHODS: Participants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE. RESULTS: Of 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28-1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270-2.395), non-nucleoside reverse transcriptase inhibitor-based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378-3.616), being cART naïve (HR, 6.046; 95% CI, 3.686-9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651-16.164). African American race (HR, 0.669; 95% CI, 0.510-0.877) and integrase strand transfer inhibitor (INSTI)-based cART (HR, 0.222; 95% CI, 0.104-0.474) were protective. CONCLUSIONS: Our findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.

Comparison of A(H3N2) Neutralizing Antibody Responses Elicited by 2018-2019 Season Quadrivalent Influenza Vaccines Derived from Eggs, Cells, and Recombinant Hemagglutinin.

BACKGROUND: Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. METHODS: Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018-2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. RESULTS: All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019-2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. CONCLUSION: Egg- and cell-derived 2018-2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.

Treatment of adults with acute uncomplicated malaria with azithromycin and chloroquine in India, Colombia, and Suriname.

BACKGROUND: To explore the use of azithromycin-chloroquine (AZCQ) for the treatment of malaria, we conducted double-blind, randomized, non-inferiority studies in India, Colombia, and Suriname comparing the combination of azithromycin 1 g and chloroquine (CQ) 600 mg base once daily (QD) for 3 days versus atovaquone-proguanil (AP) or chloroquine plus sulfadoxine-pyrimethamine (SPCQ) in adults with acute uncomplicated Plasmodium falciparum malaria. METHODS: Patients were hospitalized until three documented negative blood smears and followed through Day 42. The primary end point was parasitologic cure at Day 28. RESULTS: In India, parasite clearance rates were 84% and 94% for AZCQ and SPCQ, respectively (95% confidence interval [CI] for the difference: -22.6, 0.8). In Colombia and Suriname, parasite clearance rates were 57% and 99% for AZCQ and AP, respectively (95% CI: -52, -32). A subsequent open-label, non-comparative third study using a 2 g dose of azithromycin and 600 mg of CQ in India and Colombia resulted in an overall efficacy rate of 97%. CONCLUSION: In India, Colombia, and Suriname, 1 g azithromycin with CQ QD for 3 days was inferior to established comparator agents. An improved response rate was observed when the dose of azithromycin was increased to 2 g.

Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria.

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the in vivo efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam, Mephaquin, and Mefloquina-AC Farma) given in combination with artesunate. METHODS: Thirty-nine non-pregnant adults with P. falciparum mono-infection were randomly assigned to receive artesunate in combination with either (1) Lariam, (2) Mephaquin, or (3) Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours), 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol.Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data. RESULTS: By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14-15 days and time to maximum plasma concentration of 45-52 hours. The maximal concentration (Cmax) and interquartile range was 2,820 ng/ml (2,614-3,108) for Lariam, 2,500 ng/ml (2,363-2,713) for Mephaquin, and 2,750 ng/ml (2,550-3,000) for Mefloquina AC Farma. The pharmacokinetics of the three formulations were generally similar, with the exception of the Cmax of Mephaquin which was significantly different to that of Lariam (p = 0.04). CONCLUSION: All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.

Rapid response to a case of mumps: implications for preventing transmission at a medical research facility / Respuesta rápida a un caso de paperas: implicaciones para la prevención del contagio en una instalación de investigación biomédica

OBJECTIVE: To prevent transmission among the staff and potentially among the non-human primate (NHP) colony at the U.S. Naval Medical Research Center Detachment in Peru, where an active case of mumps was discovered in a senior laboratory technician in Sep 03, 2007. MATERIAL AND METHODS: Subjects at the research facility were interviewed and potentially susceptible contacts were tested for mumps IgG. RESULTS: In total, 81 out of 106 staff members (76 percent) had close contact with the case. Only 6/81 (7 percent) had MMR, 33 (41 percent) reported having had mumps, and 8 of 45 (18 percent) of the potentially susceptible individuals did not have immunity (IgG > 20.0). All the susceptible, exposed individuals received MMR vaccine. There were no secondary cases and access to the NHP colony was restricted. DISCUSSION: Immediate and thorough investigation and occupational health response were imperative in preventing secondary cases of mumps among humans and NHP.

OBJETIVO: Prevenir el contagio de parotiditis al personal y potencialmente a la colonia de primates no humanos (PNH), tras detectarse un caso en el personal técnico de laboratorio en el Centro de Investigación de Enfermedades de la Marina de los EUA (NMRCD). MATERIAL Y MÉTODOS: El personal fue entrevistado y se hizo una prueba de IgG para parotiditis a los contactos potencialmente susceptibles. RESULTADOS: En total, 81 de 106 miembros del personal tuvo contacto cercano con el caso. Sólo 6/81 (7 por ciento) tenían vacuna y 33 (41 por ciento) reportaron haber tenido parotiditis, y 8 de 45 (18 por ciento) de los susceptibles potenciales no tenían inmunidad (IgG > 20.0). Todos los susceptibles expuestos fueron vacunados y no hubo casos secundarios. Se restringió el acceso a la colonia de PNH. CONCLUSIÓN: La investigación inmediata y la respuesta de salud ocupacional fue imperativa para prevenir casos secundarios de parotiditis en el personal y los NHP.

Rapid response to a case of mumps: implications for preventing transmission at a medical research facility.

OBJECTIVE: To prevent transmission among the staff and potentially among the non-human primate (NHP) colony at the U.S. Naval Medical Research Center Detachment in Peru, where an active case of mumps was discovered in a senior laboratory technician in Sep 03, 2007. MATERIAL AND METHODS: Subjects at the research facility were interviewed and potentially susceptible contacts were tested for mumps IgG. RESULTS: In total, 81 out of 106 staff members (76%) had close contact with the case. Only 6/81 (7%) had MMR, 33 (41%) reported having had mumps, and 8 of 45 (18%) of the potentially susceptible individuals did not have immunity (IgG > 20.0). All the susceptible, exposed individuals received MMR vaccine. There were no secondary cases and access to the NHP colony was restricted. DISCUSSION: Immediate and thorough investigation and occupational health response were imperative in preventing secondary cases of mumps among humans and NHP.

Surveillance for adverse drug reactions to combination antimalarial therapy with sulfadoxine-pyrimethamine plus artesunate in Peru.

In 2001, Peru changed its treatment policy for uncomplicated Plasmodium falciparum malaria on the northern Pacific Coast to sulfadoxine-pyrimethamine with atresunate (SP-AS). Because Peru was the first country in the Americas to adopt this combination therapy, we established a surveillance system in the region to assess the frequency of new or worsening symptoms after starting therapy. Over a period of two years, 1,552, or approximately two-thirds of all patients with uncomplicated P. falciparum malaria who had received SP-AS on the northern coast were followed up. Of these, 8.8% reported at least one adverse effect, with the most common being vomiting, nausea, headache, abdominal pain, dizziness, and fever; no severe adverse effects related to SP-AS therapy were identified. Treatment of uncomplicated malaria with SP-AS was associated with a low frequency of mild adverse effects in Peru, and therefore should be considered as a first-line therapy in areas of the Americas where SP efficacy is still high.

Unusual pattern of Plasmodium falciparum drug resistance in the northwestern Peruvian Amazon region.

High levels of Plasmodium falciparum resistance to both chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) have been documented throughout the Amazon Basin of South America. Because of reports about the persistent efficacy of both of these drugs in the northwestern Peruvian Amazon region, we carried out an evaluation of the therapeutic efficacy of chloroquine (25 mg/kg) and SP (25 mg/kg of the sulfadoxine component) for the treatment of uncomplicated P. falciparum infections at two sites: Ullpayacu and Pampa Hermoza/Alianza. A total of 111 patients were enrolled. Only 5 (14.3%) of the 35 patients who received CQ had an adequate clinical and parasitologic response (ACPR). Six subjects (17%) had early treatment failure, 1 (2.9%) had late clinical failure, and 23 (65.7%) had late parasitologic failure (LPF). Of the subjects treated with SP, 92.3% had ACPR and 7.7% had LPF. Based on these findings, it is clear that there are at least limited areas within the Peruvian Amazon region where P. falciparum strains continue to be sensitive to SP.

Mefloquine treatment for uncomplicated falciparum malaria in young children 6-24 months of age in northern Ghana.

Mefloquine (MQ) single dose 20 mg/kg treatment of falciparum malaria was evaluated in 186 children of 6-24 months of age in northern Ghana. There were 15 RII/RIII-type parasitologic failures, all with Day 2 MQ blood levels significantly lower than children whose parasitemias cleared before Day 7 and remained clear through 28 days. Predictors of RII/RIII parasitologic response were vomiting after MQ dosing, Day 2 MQ levels < 500 ng/mL, and undetectable Day 2 levels of the carboxymefloquine metabolite. There were 50 cases of delayed RI parasitologic failure, but 71% of these cases had undetectable Day 28 blood levels of MQ and drug levels in the remaining 29% ranged below the 620 ng/mL level that suppresses MQ sensitive strains of P. falciparum. Drug levels among infants that tolerated MQ well were not associated with age, weight, hemoglobin, parasitemia, and pre-existing symptoms of vomiting or diarrhea. An observed recurrent parasitemia of 34,400 trophozoites/microL against a MQ blood concentration of 550 ng/mL was taken as indication of tolerance to suppressive levels of the drug at this location.

Outbreak of gastroenteritis at a Peruvian naval base.

In April of 2003, an outbreak of gastroenteritis was reported in a training command (Centro de Instrucción Técnica y Entrenamiento Naval (CITEN)) at a Peruvian naval base located near Lima, Peru. The Naval Medical Research Center Detachment, in collaboration with the National Peruvian Naval Hospital, conducted an investigation to determine the causative agent and potential source of the outbreak. Between April 3 and 5, 172 (16%) of 1,092 military trainees reported to the CITEN clinic with diarrhea. Of 74 trainees for whom bacterial cultures were performed, Shigella spp. were isolated from 5 (6.8%), Campylobacter spp. from 5 (6.8%), and enterotoxigenic Escherichia coli from 2 (2.7%). Pathogenic parasites were identified in 22 of 64 (34%) trainees for whom microscopic observation for ova and parasites was performed. Stool samples from asymptomatic controls could not be collected, thus we were unable to confirm that the enteropathogens isolated were the etiologic agent(s). Several food items and the hands of food handlers were contaminated with coliform bacteria and drinking water was not adequately chlorinated. Preventative measures have since reduced the number of diarrhea cases at the CITEN.

Coccidioidomycosis outbreak among United States Navy SEALs training in a Coccidioides immitis-endemic area--Coalinga, California.

An outbreak of coccidioidomycosis among 22 Navy SEALs occurred during training exercises in Coalinga, California. Ten (45%) of the 22 men had serologic evidence of acute coccidioidomycosis, the highest attack rate ever reported for a military unit. All case patients were symptomatic, and 50% had abnormal chest radiographs. There were no cases of dissemination and no deaths to date. Coccidioidomycosis continues to be a threat to military members and civilians who reside or train in areas where Coccidioides immitis, the causative agent, is endemic.

Seasonal malaria attack rates in infants and young children in northern Ghana.

The incidence density of infection and disease caused by Plasmodium falciparum in children aged six to 24 months living in the holoendemic Sahel of northern Ghana was measured during the wet and dry seasons of 1996 and 1997. At the beginning of each season, a cohort composed of 259 and 277 randomly selected children received supervised curative therapy with quinine and Fansidar and primaquine for those with normal glucose-6-phosphate dehydrogenase activity. The 20 weeks of post-therapy follow-up consisted of three home visits weekly and examination of Giemsa-stained blood films once every two weeks. Blood films were also taken from children brought to clinic with illness. The incidence density of parasitemia after radical cure was 4.7 infections/person-year during the dry season and 7.1 during the wet season (relative risk = 1.51, 95% confidence interval [CI] = 1.25-1.81; P = 0.00001). Although the mean parasitemia count at time of reinfection in the dry season (3,310/microl) roughly equaled that in the wet season (3,056/microl; P = 0.737), the risk ratio for parasitemia > 20,000/microl during the wet season was 1.71 (95% CI = 1.2-2.4; P = 0.0025). The risk ratio for parasitemia > 20,000/microl with fever during the wet season was 2.45 (95% CI = 1.5-4.1; P = 0.0002). The risk ratio for anemia (hemoglobin < 8 g/dl) at first post-radical cure parasitemia showed no difference between seasons (1.0; 95% CI = 0.73-1.4; P = 0.9915). We did not see seasonal differences in anemia known to exist in this region, probably because the longitudinal cohort design using first parasitemia as an end point prevented the subjects from developing the repeated or chronic infections required for anemia induction. These findings bear upon the design of malaria drug and vaccine trials in holoendemic areas.

Endemic infectious diseases of Afghanistan.

The current crisis in Afghanistan has resulted in an influx of Western military personnel, peacekeepers, humanitarian workers, and journalists. At the same time, unprecedented numbers of internally displaced persons and refugees have overwhelmed much of the already fragile infrastructure, setting the stage for outbreaks of infectious diseases among both foreigners and local populations. This review surveys the literature concerning the infectious diseases of Afghanistan and south-central Asia, with particular emphasis on diseases not typically seen in the Western world.