Articles from Emerging Infectious Diseases

Borna disease virus 1 (BoDV-1) causes encephalitis with a fatality rate of >90% in domestic mammals and humans. Currently, the bicolored white-toothed shrew is the only known reservoir host. We report BoDV-1 infections in 15 wild European hedgehogs from an endemic area in Germany. Because hedgehogs are distant relatives of shrews and often cared for by humans, the cases raise concern regarding a potential zoonotic risk. All the hedgehogs that tested positive for BoDV-1 died of neurological disease and exhibited severe polio-predominant lymphoplasmohistiocytic meningoencephalitis. However, because of the detection of viral antigens in nonneural cells in 1 animal, we cannot completely exclude that some infected hedgehogs shed the virus. Although direct BoDV-1 transmission is known to be inefficient, our results emphasize the necessity of hygiene measures when handling hedgehogs, especially those with neurological signs who are from BoDV-1–endemic regions.

Gestational psittacosis is a rare infectious disease caused by Chlamydia psittaci that causes high maternal and fetal mortality rates. In Japan, gestational psittacosis has been reported in 7 patients, including 4 maternal deaths without antemortem diagnosis. We molecularly diagnosed C. psittaci infection postmortem in 3 patients treated during 2017–2024. We extracted DNA from formalin-fixed paraffin-embedded placenta, lung, and spleen tissues. Analysis of multilocus sequence typing indicated sequence type (ST) 269 in 1 patient and ST335 in 2; all 3 were closely related lineages that have not been previously reported in Japan or in animals. However, the ompA gene showed distinct clusters in the phylogenetic analysis. Quantitative PCR and immunostaining revealed higher amounts of C. psittaci detected in placenta than in lung or spleen, suggesting that proliferation of C. psittaci in the placenta might cause severe symptoms. ST335/ST269 lineage could be highly virulent strains for pregnant women.

Diagnosis of coccidioidomycosis is challenging and requires a high index of clinical suspicion. We estimated the incidence and duration of, and risk factors associated with, diagnostic delays and missed opportunities in the diagnosis of coccidioidomycosis. We conducted a retrospective analysis of health insurance claims data in the United States during 2001–2022 included in the Merative MarketScan Databases. Using a case-crossover design and a bootstrapping approach, we estimated the number of excess visits for coccidioidomycosis-related symptoms before diagnosis. We also evaluated potential factors associated with delay. We estimated that almost 60% of patients experienced >1 missed opportunity for diagnosis; the average diagnostic delay was 29.69 (95% CI 28.25–31.18) days. Missed opportunities were predominantly observed in outpatient settings (73%) and were significantly associated with older age, rural residence, underlying pulmonary conditions, and prescriptions for antibiotics or inhalers. Diagnostic delays for coccidioidomycosis are common, and addressing such delays could improve clinical outcomes.

Malaria transmission at the human–wildlife interface remains poorly characterized in the Amazon. We conducted a molecular survey of Plasmodium spp. in an Indigenous community (n = 141) and sympatric nonhuman primates (NHPs) (n = 341; 10 species) in the Peruvian Amazon during 2007–2020. By using nested or quantitative PCR (targeting cytb, cox3, and 18S rRNA genes) and sequencing, we estimated prevalence, parasite load, and genetic similarity. We detected Plasmodium in 43.3% of humans and 51.9% of NHPs. P. vivax/simium predominated in humans (42.1%), whereas P. brasilianum/malariae predominated in NHPs (24.6%). P. falciparum was rare in both hosts. Children <8 years of age showed higher parasite load than older persons. Bayesian phylogenies revealed >99.9% identity among human and NHP lineages, supporting shared Plasmodium lineages. NHP lineages showed low interannual variation. One third of human infections were asymptomatic. Our findings reveal hidden reservoirs and support integrating wildlife surveillance into Amazon malaria elimination strategies.

Dengue is not endemic in the continental United States; most cases occur in returning travelers. During August–November 2024, a total of 14 locally acquired cases of dengue were identified in Los Angeles County, California, USA. Epidemiologic evidence indicates that locally acquired cases occurred in several neighborhoods, suggesting short transmission chains after introductions from returning travelers. In one neighborhood, evidence supported ongoing transmission for up to 7 weeks. Median patient age was 54 (range 5–79) years; 8 (57%) patients were female and 6 (43%) male, and 6 (43%) required hospitalization. Delays in healthcare seeking and diagnoses were noted; median time from symptom onset to specimen collection for dengue testing was 9 (range 2–34) days. Local dengue transmission in Los Angeles County highlights the emerging threat of mosquitoborne disease transmission in nonendemic areas and the need for rapid and coordinated public health and vector control responses to interrupt transmission.

The multidrug-resistant yeast Candida (Candidozyma) auris has caused several healthcare-associated outbreaks in the United States. We provide a genomic epidemiologic description of 1,535 C. auris isolates collected in the United States during 2013–2022. We identified clades I, II, III, and IV but not clades V or VI. Median pairwise single-nucleotide polymorphism distances indicated lower intraclade relatedness for clades I (91), III (43), and IV (43), compared with clade II (1,455). Phylogenetic analysis showed regional clusters with varying predominant clades. Of 809 isolates that underwent antifungal susceptibility testing, 53 were echinocandin resistant, distributed across 3 clades; 92% (49/53) had FKS1 hotspot mutations, which varied regionally. Our findings corroborate ongoing transmission and clonal expansion of C. auris, likely propagated by multiple introductions within and between geographic regions. Echinocandin resistance in multiple clades highlights the need to increase awareness, improve treatment practices, and engage in rapid public health response.

We conducted a retrospective phylogenetic analysis of Mayaro virus (MAYV) detected in French Guiana during 1996–2024. Analysis revealed circulation of MAYV genotype D sublineage 2 and suggested introduction from Brazil and spread to Haiti and Venezuela. Phylogenetic findings support endemic circulation and reinforce the need for MAYV surveillance in the region.

We developed and validated a real-time PCR to detect an Anaplasma bovis–like agent. We applied that assay to 672 Dermacentor spp. ticks collected from across the United States and found 0.1% A. bovis–like agent prevalence. This assay could enhance epidemiologic surveys for this A. bovis–like agent in ticks and humans.

Human tick-borne relapsing fever caused by Borrelia persica is common in western Asia. A survey of 301 horses in Israel revealed 9.96% seropositivity toward B. persica antigens; 1 horse (0.33%) was also PCR positive for B. persica DNA. Phylogenetic analysis supported a transmission cycle involving ticks, humans, and horses.

Pigeon paramyxovirus type 1 (PPMV-1) is a genotype of avian paramyxovirus type 1 that uses species of the family Columbidae as reservoir species. We report fatal PPMV-1 encephalitis in a human without immunosuppression or travel history outside metropolitan France. Postmortem analyses revealed PPMV-1 in tissues, underscoring that physicians should consider this potential diagnosis.

Yezo virus is an emerging tickborne orthonairovirus. We detected Yezo virus RNA in tick bite patients and in Ixodes persulcatus ticks in west Siberia and Far East, Russia. Clinicians should consider the expanded area of Yezo virus identification and the I. persulcatus tick habitat when evaluating patients after tick bites in Russia.

We analyzed tissue and serum samples from 124 wild animals from communities with confirmed mpox cases in Nigeria. Tissue samples were PCR-negative, but serum samples from 8 animals (6.45%)—3 feral cats, 4 giant pouched rats, and 1 shrew—revealed Orthopoxvirus antibodies, suggesting these species as probable reservoirs.

We investigated an outbreak of unknown respiratory disease and 8 deaths among older adults in a long-term care facility in France. We identified human rhinovirus (HRV) by quantitative PCR and HRV-B14 by metagenomics. We obtained 5 HRV-B14 genomes that diverged from 5 publicly available genomes. Real-time metagenomics could enable rapid clinical diagnoses.

We report a case of Cryptosporidium sp. OTUi identified in a tourist from Denmark who recently traveled to Indonesia. Previous detections include a traveler from Australia returning from Bali, a bat from the Philippines, and a patient from Australia. On the basis of those findings, we believe zoonotic transmission is plausible.

In autumn 2025, highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus, genotype EA-2024-DI.2.1, caused systemic infections leading to a mass mortality event among the western migrating subpopulation of Eurasian cranes (Grus grus) in Germany. Gregarious behavior at feeding and resting sites likely promoted rapid viral spread within the population.

We report Sin Nombre virus (SNV) genome sequences in the northwestern United States, including SNV sequences recovered from montane voles. Analysis of samples collected from 189 individual rodents revealed high SNV prevalence in the region and evidence of virus reassortment or coinfection, highlighting ongoing virus diversification in rodents.

We tested wild ruminants, boar, and carnivores in northeast Germany for highly pathogenic avian influenza subtype H5 antibodies. Wild ruminants were seronegative, but 3.5% of boar and 12.5%–21.9% of carnivores were seropositive, indicating frequent spillover. Because such events might accelerate mammalian (and ultimately human) adaptation, sustained monitoring remains essential.

Replication of influenza A virus in human nasal epithelium affects transmissibility and disease. We compared virus replication and immune responses in human nasal epithelium infected with seasonal and highly pathogenic avian influenza A(H5N1) viruses. Contemporary H5N1 viruses replicated better than the historical isolate; however, interferon response to B3.13 genotype viruses was dampened.

In 2024, influenza A(H5N1) genotype B3.13 viruses emerged from cattle and caused mild spillover infections in humans. Using human bronchus and lung tissue, we evaluated tropism, replication, and pathogenesis of 2 cattle influenza isolates. Those viruses showed moderate replication competence and induced robust proinflammatory responses, suggesting potential risk for human health.

We estimated an unmitigated mean serial interval during a school-based pertussis outbreak in South Korea at 14.7 (95% credible interval 9.0–27.4) days, comparable with previous estimates. Public health interventions reduced the effective reproduction number by 65% (95% credible interval 26%–88%), which likely brought it to <1 and contributed to curbing the outbreak.

We detected herpes simplex virus 1 in the trigeminal ganglia of trafficked Neotropical primates (1 Aotus azarai; 3 Sapajus macrocephalus) in Peru. Tests also revealed Saimiriine alphaherpesvirus 1 in the trigeminal ganglia of 2 Saimiri sp. monkeys. Our findings suggest latency and raise concerns about diagnostic standards, viral reactivation, and spillover risks.

We describe a case of endocarditis and aortic root abscess caused by Bartonella clarridgeiae bacteria in a patient in Australia. The patient initially sought care for leg pain and was found to have bilateral tibioperoneal trunk mycotic aneurysms. 16S rRNA PCR on excised aneurysm tissue identified the cause as B. clarridgeiae.

We obtained 5 isolates of Borrelia turicatae from ticks captured in a public park in Aguascalientes, Mexico. A serologic survey in resident fauna showed antibodies against B. turicatae. Relapsing fever borrelias are present in Ornithodoros turicata ticks and circulate in a zoonotic cycle, posing a risk for human infection.

Strengthened in-country sequencing generated 28 Lassa virus genomes from human clinical cases in Guinea, expanding knowledge of Lassa fever in the country. Phylogeographic analysis revealed cross-border exchange between Liberia and the N’Zérékoré region and a Sierra Leone introduction into Guéckédou. Enhanced genomic surveillance is crucial to guide public health.

Since March 2024, highly pathogenic avian influenza (HPAI) A(H5N1) virus has infected dairy cattle in the United States, prompting concern about novel transmission routes. During an outbreak in California, HPAI H5N1 RNA was detected in an asymptomatic bull’s semen. Although infectious virus was not isolated, semen-associated transmission risks and biosecurity practices remain a concern.

We analyzed respiratory syncytial virus genome sequences from adults in Georgia, USA, during 2024–2025. We found multiple co-circulating lineages of both A and B subtypes. We identified few mutations in F protein antigenic sites in this population with low vaccine uptake, highlighting the need for ongoing genomic surveillance.

Diagnosis of coccidioidomycosis is challenging and requires a high index of clinical suspicion. We estimated the incidence and duration of, and risk factors associated with, diagnostic delays and missed opportunities in the diagnosis of coccidioidomycosis. We conducted a retrospective analysis of health insurance claims data in the United States during 2001–2022 included in the Merative MarketScan Databases. Using a case-crossover design and a bootstrapping approach, we estimated the number of excess visits for coccidioidomycosis-related symptoms before diagnosis. We also evaluated potential factors associated with delay. We estimated that almost 60% of patients experienced >1 missed opportunity for diagnosis; the average diagnostic delay was 29.69 (95% CI 28.25–31.18) days. Missed opportunities were predominantly observed in outpatient settings (73%) and were significantly associated with older age, rural residence, underlying pulmonary conditions, and prescriptions for antibiotics or inhalers. Diagnostic delays for coccidioidomycosis are common, and addressing such delays could improve clinical outcomes.

Snowshoe hare virus (SSHV) is an arbovirus in the California serogroup known to circulate throughout Canada and northern latitudes of the United States. The clinical spectrum of SSHV infection ranges from asymptomatic or mild febrile illness to neuroinvasive disease; neuroinvasive disease occurs more often in children and young adults. We describe a cluster of confirmed and probable SSHV meningoencephalitis cases in 3 children from Whistler, British Columbia, Canada, in the summer of 2024. We highlight the shared epidemiology, clinical manifestations, serologic diagnostic methods, and outcomes for the cases. All 3 children acquired the infection locally and made a full recovery. This case series suggests underrecognized SSHV infection prevalence that warrants enhanced surveillance and review of existing diagnostic algorithms. California serogroup viruses, including SSHV, should be recognized as a potential cause of neuroinvasive disease in North America during mosquito season, particularly when initial diagnostic testing is inconclusive.

Blastomyces urine antigen testing is a sensitive blastomycosis diagnostic method, but its utility for active case identification during outbreaks is unknown. We evaluated urine antigen testing for identifying blastomycosis cases during a 2023 outbreak at a Michigan, USA, paper mill and assessed demographic and clinical factors associated with test positivity. Approximately 2 months after the outbreak was recognized, we collected work and health information for 603 employees; 95% (n = 578) underwent urine antigen testing and 9% (n = 52) tested positive, including 25 previously undetected cases. Blastomycosis-like symptoms were associated with test positivity (p<0.001), but 10% of employees with positive results were asymptomatic. Recent hospitalization for blastomycosis was associated with test positivity (p = 0.02) and higher antigen levels. Further research into urine antigen testing is needed clarify its suitability for detecting mild and asymptomatic infections during outbreak investigations. Urine antigen testing had high acceptability among employees and effectively identified additional cases.

Reports of ocular manifestations of Lyme disease (LD) are uncommon, and signs and symptoms may be overlooked by physicians. We conducted a retrospective case series of ocular LD reported during 1988–2025. Among 27 published reports in PubMed, we noted that, in 38 cases, the most common ocular manifestation was uveitis, representing 45% of cases, followed by optic neuritis and cranial nerve palsies (including trochlear and abducens). Not all cases met Centers for Disease Control and Prevention surveillance guidelines for LD, given that some case reports were published before the current guidelines. Cases that provided microbiologic proof were 2 anterior uveitis cases, 1 case of anterior uveitis with abducens’s nerve palsy, 1 case of intermediate uveitis, and 1 case of intranuclear ophthalmoplegia. Ocular LD can have a broad variety of manifestations; therefore, physicians should be aware of those manifestations and obtain microbiologic proof for a more definitive diagnosis and epidemiologic value when possible.

Group A Streptococcus (GAS) causes a variety of diseases in humans but is not widely appreciated as a cause of meningitis. During 1997–2022, ten sites participating in the Active Bacterial Core Surveillance network in the United States identified GAS meningitis cases. We calculated annual incidence and case-fatality rates (CFRs) for 320 of those cases and determined antimicrobial resistance by whole-genome sequencing. Annual incidence of GAS meningitis ranged from 0.02 to 0.07 cases/100,000 persons. Children <1 year of age had the highest average annual incidence, 0.23 cases/100,000 children. GAS meningitis had a higher CFR (19.4%) than meningitis caused by group B Streptococcus, Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae. Clindamycin resistance among GAS meningitis isolates increased from 3.2% during 1997–2002 to 17.7% during 2018–2022. Clinicians should be aware that meningitis is an uncommon but severe manifestation of invasive GAS and has a higher CFR than more established meningitis etiologies.

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We analyzed pregnancy outcomes of women who became pregnant during the study. Among 740 women, 97 (13.1%) became pregnant. Of 102 pregnancies (in 97 participants), 30 (29.4%) participants were exposed to study drugs. Fetal loss was reported for 3/13 (23.1%) in the control regimen, 1/9 (11.1%) in the rifapentine/moxifloxacin regimen, and 1/8 (12.5%) in the rifapentine regimen. Among 21 live births in exposed pregnancies (7 in each arm), 1 infant with a congenital anomaly was reported in a participant on the rifapentine regimen. Among women receiving a short rifapentine/moxifloxacin regimen for tuberculosis who became pregnant, we observed no elevated rates of fetal losses or congenital anomalies.

Haematospirillum jordaniae was first identified as a human pathogen in 2016. In this article, we describe 4 patients who had H. jordaniae infections identified in 2020 and who had temporally and spatially linked environmental exposures. Three of the 4 patients reported leg injuries while participating in recreational river water activities in south-central Pennsylvania, USA. In 2024, we detected H. jordaniae in river samples collected at locations identified during patient interviews. All patients sought emergency department services for clinical assessment; however, the causative bacterial isolate was not initially identified. H. jordaniae was identified as the bacterial cause months after patient treatment and discharge. Although H. jordaniae infections are considered rare, the true occurrence is unknown. Additional information about the organism’s ecology and environmental seasonality could guide public health messaging and increase awareness among healthcare providers.

Reptile-associated outbreaks of human Salmonella infections are increasing in Canada, coinciding with a rise in the popularity of reptiles as pets. We conducted a retrospective analysis of surveillance data for human Salmonella case-patients in Ontario during 2015–2022. We compared serotypes and reptile types for those reporting domestic reptile or amphibian exposure with veterinary Salmonella isolates reported during the same period. Case-patients commonly reported contact with reptile types from which Salmonella was most frequently isolated. Some serotypes from human case-patients were closely associated with contact with specific reptile types, including Salmonella Paratyphi B biovar Java (Salmonella Paratyphi B variant L (+) tartrate +) with snakes, Salmonella Agbeni with turtles, and Salmonella Cotham, Salmonella Chester, and Salmonella Tennessee with bearded dragons. Salmonella was most likely to be reported from reptiles fed a carnivorous diet. Education of reptile owners could help promote proper veterinary care and reduce transmission of zoonotic infections.

Candida bloodstream infections, and their increasing antifungal resistance, are a global concern. In this cross-sectional study, we analyzed 2,443 culture-confirmed candidemia cases reported in South Africa during 2012–2017 to assess the effect of previous antifungal exposure on nonsusceptible Candida infection. We classified cases by species resistance profile and patient’s antifungal use within 14 days before infection. We found that 48% of cases were caused by nonsusceptible species, and 20% of patients had prior antifungal exposure, mainly to fluconazole. In patients >90 days of age, prior antifungal use was significantly associated with nonsusceptible Candida bloodstream infection (adjusted OR 2.02, 95% CI 1.43–2.87; p<0.001), with species-specific effects. No such association was found in neonates and young infants, for whom hospital transmission appeared more influential. Our findings underscore the need for targeted antifungal stewardship and enhanced infection prevention to mitigate antifungal resistance in South Africa.

The complexity of rickettsial serodiagnostics during acute illness has limited clinical characterization in Africa. We used archived samples from sepsis (n = 259) and acute febrile illness (n = 70) cohorts in Uganda to identify spotted fever and typhus group rickettsiae by using immunofluorescence assay and clinically validated rRNA reverse transcription PCR (RT-PCR). Among 329 participants, 10.0% had rickettsial infections (n = 33; n = 20 identified with immunofluorescence assay and n = 13 by RT-PCR). Serum rRNA RT-PCR was 75.0% (95% CI 42.8–94.5%) sensitive and 91.2% (95% CI 85.8–95.1%) specific. Thrombocytopenia was more common among patients with rickettsial infections than with other nonmalarial infections (adjusted odds ratio 3.7; p = 0.003). No participants were on a tetracycline antimicrobial drug at admission. rRNA RT-PCR is a promising diagnostic strategy for identifying acute rickettsial infections. Doxycycline should be included in empiric antimicrobial drug regimens for nonmalarial febrile illness in this region.

Prevalence of emerging fungal infections is increasing, particularly among immunocompromised persons, children, and older persons. We report 108 cases of Scheffersomyces spartinae infection in pediatric patients from Karachi and other cities in Pakistan, of which 107 were identified from blood cultures. Cultures were initially misidentified as Clavispora lusitaniae by a biochemical assay before speciation as S. spartinae by whole-genome sequencing. All isolates were from children <12 years of age, and >69% were from children <1 month of age. Isolates were genetically distinct across regions of Pakistan; however, genetic diversity was low in isolates from patients in Karachi and nearby Nawabshah and had median differences of just 9 pairwise nucleotide variants. This study demonstrates S. spartinae is a potentially emerging pathogen in neonates and young infants in Pakistan. The findings highlight the limitations of phenotypic identification for detecting emerging fungal infections and underscore the value of molecular identification approaches.

Mpox was first identified against the backdrop of the smallpox eradication campaign. Monkeypox virus (MPXV), the causative agent of mpox, has been maintained in animal reservoirs in the forested regions of West and Central Africa as 2 distinct clades; clade I has historically caused more severe infection in Central Africa than clade II, historically found in West Africa. However, rapid reemergence and spread of both MPXV clades through novel routes of transmission have challenged the known characteristics of mpox. We summarize mpox demographic distribution, clinical severity, and case-fatality rates attributed to genetically distinct MPXV subclades and focus on MPXV clade Ib, the more recently identified subclade. Broad worldwide assistance will be necessary to halt the spread of both MPXV clades within mpox endemic and nonendemic regions to prevent future outbreaks.

Talaromycosis is a life-threatening fungal disease that primarily affects immunocompromised persons in Southeast Asia. We conducted a multicenter, case–control study recruiting participants with advanced HIV disease in Vietnam; 205 case-patients with culture-confirmed talaromycosis were matched to 405 control-patients by age, sex, and CD4 count. Occupational exposure to tropical plants (odds ratio [OR] 1.73 [95% CI 1.10–2.73]; p = 0.017) and to farmed animals (OR 2.07 [95% CI 1.20–3.55]; p = 0.009) were independent risk factors for talaromycosis. Talaromycosis risk was higher in participants from highland regions than in persons from lowland regions (p<0.05). Participants from lowland regions who had lived or traveled to highland regions had a higher risk for talaromycosis (OR 3.15 [95% CI 1.49–6.64]; p = 0.003). This study confirms the epidemiologic correlation between talaromycosis and soil exposure and demonstrates an epidemiologic link between talaromycosis and residence in or travel to highland regions of Vietnam.

Spiroplasma ixodetis has been reported to cause the rare combination of cataract and uveitis in infants. Through a retrospective analysis of available literature and additional unpublished cases, we identified 28 eyes from 18 infants from 8 countries in Europe with cataracts and intraocular inflammation. The cataracts were bilateral in 55.6%, unilateral in 44.4%, and progressive in 46.4% of patients. Granulomatous anterior uveitis was found in all infants. Presence of S. ixodetis was supported by PCR (positive in 89.3% of eyes tested), transmission electron microscopy (positive in 90% of eyes tested), or culture of aspirated lens material (positive in 87.5% of eyes tested). Treatment with macrolide antimicrobial drugs, corticosteroids, and lensectomy appeared to be effective. Two patients had a recurrence of the uveitis after lens extraction and needed prolonged treatment. To increase awareness of S. ixodetis, we suggest its inclusion with the organisms of the TORCH acronym.

During 2007–2020, we conducted a cross-sectional prevalence study among patients with acute undifferentiated febrile illness to describe the burden and long-term epidemiology of rickettsioses in Cambodia. Serum samples were collected from 10,243 participants, along with epidemiologic data, information on clinical symptoms, demographic characteristics, and risk factors. A total of 802 (7.8%) participants met the definition for acute rickettsial infection after ruling out malaria, influenza, dengue, and chikungunya; 557 (5.4%) cases were typhus, 154 (1.5%) spotted fever, and 136 (1.3%) scrub typhus. Overall seroprevalence was 18.1% (1,857/10,243). Increased age, residence in urban settings, and recent travel to forests were significantly associated with rickettsial infection. Symptoms significantly associated with infection included rash, vomiting, and skin lesions. Our results confirm the underlying burden of rickettsioses and associated risk factors in Cambodia and highlight the need for accessible diagnostics and clinical guidance that consider rickettsioses when treating persons with acute undifferentiated febrile illness.