Effects of HIV infection and/or malaria on maternal and neonatal health in a high-prevalence setting.

OBJECTIVE: HIV infection and malaria have been associated with different complications during pregnancy and delivery. HIV-positive pregnant women are at increased risk for all adverse outcomes of malaria during pregnancy. The main objective was to analyse the obstetric and perinatal consequences of malaria, HIV infection and HIV/malaria co-infection in pregnant women and newborns, which has been less well evaluated. METHODS: A cross-sectional study was carried out in the Maternity Service of the Provincial Hospital of Tete Mozambique, involving completion of a structured questionnaire that included demographic data, and information on the current pregnancy, delivery and the newborn. In total, 819 women (13-45 years old) in the immediate postpartum period were enrolled between 1 March and 31 October 2016. RESULTS: The overall prevalence of HIV and malaria, considered separately, in pregnant women was ~12% (103 women with HIV and 101 with malaria). Only one-fifth of HIV-infected women knew their HIV status before pregnancy. A significantly higher proportion of women with HIV attended four or more antenatal care visits than women without HIV. Caesarean section was less frequent in HIV patients, and peripartum urinary infection was more frequent than in seronegative women (13/103 [12.6%] vs. 34/716 [4.7%]). HIV/malaria co-infection were 17/819 (2%) and was significantly associated with the development of pre-eclampsia when HIV-infected patients received anti-retroviral treatment, and with an increase in urinary tract infections around delivery. With respect to the newborn, co-infection increased the frequency of early neonatal death, as well as neonatal asphyxia and jaundice. CONCLUSIONS: In Mozambique, the prevalence of malaria and HIV infection in women of childbearing age continues to be high and contributes additively to complications during pregnancy and childbirth, and in the newborn. Therefore, integrating HIV, malaria and reproductive health services is essential if maternal and foetal outcomes are to improve.

Increased peripartum mortality associated with maternal subclinical malaria in Mozambique.

BACKGROUND: Plasmodium falciparum infection in pregnant women in sub-Saharan Africa is often asymptomatic. As these forms of malaria are often submicroscopic and difficult to diagnose by conventional methods (microscopy and/or rapid diagnostic test), diagnosis requires the use of molecular techniques such as polymerase chain reaction (PCR). This study analyses the prevalence of subclinical malaria and its association with adverse maternal and neonatal outcomes, a topic that has been scarcely evaluated in the literature. METHODS: A cross-sectional study was conducted using semi-nested multiplex PCR to assess the presence of P. falciparum in placental and peripheral blood of 232 parturient pregnant women at the Hospital Provincial de Tete, Mozambique between March 2017 and May 2019. Multivariate regressions were performed to assess the associations of maternal subclinical malaria with several maternal and neonatal outcomes after controlling for the presence of preeclampsia/eclampsia (PE/E) and HIV infection, as well as for other maternal and pregnancy characteristics. RESULTS: In total, 17.2% (n = 40) of the women studied had positive PCR for P. falciparum (7 in placental blood only, 3 in peripheral blood only). We found a significant association between subclinical malaria and a higher peripartum mortality risk, which persisted after controlling for maternal comorbidity and maternal and pregnancy characteristics (adjusted odds ratio: 3.50 [1.11-10.97]). In addition, PE/E and HIV infections were also significantly associated with several adverse maternal and neonatal outcomes. CONCLUSION: This study demonstrated the association of subclinical malaria, as well as of PE/E and HIV, in pregnant women with adverse maternal and neonatal outcomes. Therefore, molecular methods may be sensitive tools to identify asymptomatic infections that can reduce the impact on peripartum mortality and their contribution to sustained transmission of the parasite in endemic countries.

Murine Typhus in Canary Islands, Spain, 1999-2015.

To document the epidemiology, clinical features, and outcomes of murine typhus patients in the Canary Islands (Spain), we analyzed data that were retrospectively collected for 16 years for 221 patients. Murine typhus in the Canary Islands is characterized by a high rate of complications (31.6%), mainly liver, lung, kidney or central nervous system involvement.

Epidemiological of cat scratch disease among inpatients in the Spanish health system (1997-2015).

Cat scratch disease, whose causative agent is Bartonella henselae, is an anthropozoonosis with a worldwide distribution that causes significant public health problems. Although it is an endemic disease in Spain, the available data are very limited. The aim of our study was to describe cat scratch disease inpatients in the National Health System (NHS) of Spain. This was a retrospective descriptive study using the minimum basic data set (CMBD in Spanish) in patients admitted to hospitals of the NHS between 1997 and 2015 with a diagnosis of cat scratch disease (ICD-9: 078.3). We found 781 hospitalized patients diagnosed with cat scratch disease. The mean age (± SD) was 30.7 ± 25.3 years old. The male/female ratio was 1.1:1. The incidence rate over the study period was 0.93 (95% CI, 0.86-0.99) cases per million person-years. The incidence rate in men was 0.98 cases per million person-years and that in women was 0.88 cases per million person-years. The cases were more frequent from September to January. A total of 652 (83.5%) cases were urgent hospital admissions. The average hospital stay was 8.4 ± 8.9 days. The overall lethality rate of the cohort was 1.3%. We have demonstrated that CSD causes a substantial burden of disease in Spain, affecting both adult and pediatric patients with a stable incidence rate. Our data suggest that CSD is benign and self-limited, with low mortality, and its incidence is possibly underestimated. Finally, there is a need for a common national strategy for data collection, monitoring, and reporting, which would facilitate a more accurate picture and the design of more strategic control measures. Hospital discharge records (HDRs) could be a good database for the epidemiological analysis of the hospital management of CSD.

Epidemiological assessment of 5598 brucellosis inpatients in Spain (1997-2015).

Brucellosis remains one of the main zoonoses worldwide. Epidemiological data on human brucellosis in Spain are scarce. The objective of this study was to assess the epidemiological characteristics of inpatient brucellosis in Spain between 1997 and 2015. A retrospective longitudinal descriptive study was performed. Data were requested from the Health Information Institute of the Ministry of Health and Equality, which provided us with the Minimum Basic Data Set of patients admitted to the National Health System. We also obtained data published in the System of Obligatory Notifiable Diseases. A total of 5598 cases were registered. The period incidence rate was 0.67 (95% CI 0.65-0.68) cases per 100 000 person-years. We observed a progressive decrease in the number of cases and annual incidence rates. A total of 3187 cases (56.9%) came from urban areas. The group most at risk comprised men around the fifth decade of life. The average (±s.d.) hospital stay was 12.6 days (±13.1). The overall lethality rate of the cohort was 1.5%. The number of inpatients diagnosed with brucellosis decreased exponentially. The group of patients with the highest risk of brucellosis in our study was males under 45 years of age and of urban origin. The lethality rate has reduced to minimum values. It is probable that hospital discharge records could be a good database for the epidemiological analysis of the hospital management of brucellosis and offer a better information collection system than the notifiable diseases system (EDO in Spanish).

Zika Virus Screening among Spanish Team Members After 2016 Rio de Janeiro, Brazil, Olympic Games.

We evaluated the risk for the Spanish Olympic Team acquiring Zika virus in Rio de Janeiro, Brazil, during 2016. We recruited 117 team members, and all tested negative for Zika virus. Lack of cases in this cohort supports the minimum risk estimates made before the Games.

Usefulness of the early molecular diagnosis of Q fever and rickettsial diseases in patients with fever of intermediate duration. / Utilidad del diagnóstico molecular precoz de fiebre Q y rickettsiosis en pacientes con fiebre de duración intermedia.

Most cases of fever of intermediate duration (FDI) in Spain are associated with infectious diseases (mainly Q fever and rickettsia infections). In clinical practice, the causal diagnosis of these entities is based on immunodiagnostic techniques, which are of little help in the early stages. Therefore, the aim of this study was to evaluate the usefulness of molecular techniques for the early diagnosis of Q fever and rickettsia diseases in patients with FDI. A PCR method was used to detect the presence of genetic material of Coxiella burnetii and Rickettsia spp. in blood specimens from 271 patients with FDI. The specificity of both techniques is high, allowing diagnosis in cases undiagnosed by specific antibodies detection. These data suggest that the use of molecular techniques, with proper selection of the study specimen, and using appropriate primers is a useful tool in the early diagnosis of the main causes of FDI, especially if serology is negative or inconclusive.

Relationship of polychlorinated biphenyls (PCBs) with parasitism, iron homeostasis, and other health outcomes: Results from a cross-sectional study on recently arrived African immigrants.

Polychlorinated biphenyls (PCBs) are toxic and persistent chemicals produced between 1930s and 1980s, which accumulate in humans and wildlife. Although a decreasing trend of PCB levels in humans has been described in developed countries, mainly as a consequence of strict regulations and remediation plans, an inverse trend has been recently reported in people from developing countries. We had the opportunity of sampling a series of African immigrants recently arrived to the Spanish archipelago of the Canary Islands, in which high levels of PCBs have been described, and we studied the relationships between their level of contamination and health status. A total of 570 subjects who underwent a complete medical examination and a face-to-face interview were recruited for this study. Hematological and biochemical parameters (blood and urine) were determined in all participants. Serology for the diagnostic of infectious diseases was also performed, and direct identification of parasites was performed in feces, urine or blood samples when appropriate. It is remarkable that up to 26.0% of the population had intestinal parasites, and we found an inverse relationship between PCB levels and parasitism and parasitic diseases: median values of PCBs were lower in parasitized subjects than in subjects without parasites in stool (237.6ng/g fat vs. 154.4ng/g fat for marker PCBs, p=0.015) and median values of dioxin-like PCBs were lower in subjects carrying pathogen parasites than among subjects showing non-pathogen parasites in stool (0.0 ng/g fat vs. 13.1ng/g fat, respectively; p=0.001). Although this inverse association had been described in some vertebrates this is the first study reporting such an association in humans. Furthermore, it has been also recently described that PCBs may disrupt iron metabolism, and we found a direct relationship between serum iron and total PCBs burden (r=0.231, p=0.025), suggesting that PCBs, although at subclinical level, could play a role on iron homeostasis. Although the role of PCBs in parasitism and in the iron metabolism needs future research, our findings may help to understand the adverse health outcomes associated to environmental exposure to PCBs and they might be used in exposed populations as indicators of subtle effects due to environmental insult.

[Population screening strategies in recent immigrant to Spain]. / Estrategias de cribado en población inmigrante recién llegada a España.

The definition of terms that delimites the content of this paper are initially displayed. Subsequently, the main sources of information about the disease screening in immigrants and the entities considered susceptible of screening are showed. In a later section we review the diagnostic methodology used, separately considering the history, physical examination, the usual complementary tests and specific studies of both infectious and noninfectious diseases. Finally, with the limitations of the data available a proposal of a protocol for screening of diseases in recent immigrant is performed.

Executive summary: Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.

Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.

[Diagnosis and treatment of imported malaria in Spain: Recommendations from the Malaria Working Group of the Spanish Society of Tropical Medicine and International Health (SEMTSI)]. / Diagnóstico y tratamiento de la malaria importada en España: recomendaciones del Grupo de Trabajo de Malaria de la Sociedad Española de Medicina Tropical y Salud Internacional (SEMTSI).

Malaria is a common parasitic disease diagnosed in the returned traveler. Mortality in travelers with imported malaria is around 2-3%, and one of the main factors associated with poor prognosis is the delay in the diagnosis and treatment. Imported malaria cases usually present with fever, headache and myalgia, but other symptoms may appear. The diagnosis should be performed as soon as possible, using thick smear or rapid diagnostic tests, and a blood smear. Treatment should be initiated urgently. In cases of severe malaria, the use of intravenous artemisinins has proved to be superior to intravenous quinine. This document reviews the recommendations of the expert group of the Spanish Society of Tropical Medicine and International Health (SEMTSI) for the diagnosis and treatment of imported malaria in Spain.

Toxoplasma gondii Infection in Humans: A Comprehensive Approach Involving the General Population, HIV-Infected Patients and Intermediate-Duration Fever in the Canary Islands, Spain.

A prior investigation in 1993 identified a high seroprevalence of toxoplasmosis (63%) in the Canary Islands. This study aims to assess the current prevalence of the disease in diverse population groups. The study was based on a population-scale screening involving 273 residents utilizing T. gondii IgG ELISA and a 20 year retrospective study (1998-2018). This included AIDS/HIV outpatients (1357, of which 324 were residents), AIDS/HIV hospitalized patients (741) and patients with fever of intermediate duration (158). The seroprevalence in the resident population was 37%, with significant differences between islands. Among resident outpatients with AIDS/HIV, 14.2% had specific anti-T. gondii IgG, and three had anti-T. gondii IgM; however, IgG avidity testing indicated non-active infection. In patients hospitalized for AIDS/HIV, T. gondii causing encephalitis was detected in 2%. Among patients with fever of intermediate duration, 28.5% were positive for T. gondii IgG, and four also showed IgM positivity, although the infection was non-active. The study reveals a decrease in human toxoplasmosis over the past 30 years. However, the current seroprevalence, which stands at 37%, together with the substantial risk that T. gondii represents for immunocompromised individuals, highlights the need to implement preventive and control strategies to control the threat that this infection can pose to public health in the Canary Islands population.

Partial recessive IFN-γR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds.

We report a series of 14 patients from 11 kindreds with recessive partial (RP)-interferon (IFN)-γR1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875-2950) and 500 (200-1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-γR1 levels and residual response to IFN-γ. The patients suffered from bacillus Calmette-Guérin-osis (n= 6), environmental mycobacteriosis (n= 6) or tuberculosis (n= 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 ± 9.13 years. Thirteen patients survived until the age of 14.82 ± 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-γR1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases.

Seroprevalence of Strongyloides stercolaris in Patients about to Receive Immunosuppressive Treatment in Gran Canaria (Spain).

Strongyloides stercoralis infection is generally asymptomatic or mildly symptomatic, but in the immunosuppressed host, it is associated with more severe and complicated forms with a worse prognosis. S. stercoralis seroprevalence was studied in 256 patients before receiving immunosuppressive treatment (before kidney transplantation or starting biological treatments). As a control group, serum bank data of 642 individuals representative of the population of the Canary Islands were retrospectively analyzed. To avoid false positives due to cross-reactivity with other similar helminth antigens present in the study area, IgG antibodies to Toxocara spp. and Echinococcus spp. were evaluated in cases positive for Strongyloides. The data show this is a prevalent infection: 1.1% of the Canarian population, 2.38% of Canarian individuals awaiting organ transplants and 4.8% of individuals about to start biological agents. On the other hand, strongyloidiasis can remain asymptomatic (as observed in our study population). There are no indirect data, such as country of origin or eosinophilia, to help raise suspicion of the disease. In summary, our study suggests that screening for S. stercoralis infection should be performed in patients who receive immunosuppressive treatment for solid organ transplantation or biological agents, in line with previous publications.

Executive summary consensus statement of imported diseases group (GEPI) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SETMSI), on the diagnostic and treatment of imported schistosomiasis.

Schistosomiasis is a highly prevalent disease, especially in immigrant populations, and is associated with significant morbidity and diagnostic delays outside endemic areas. For these reasons, the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SEMTSI) have developed a joint consensus document to serve as a guide for the screening, diagnosis and treatment of this disease outside endemic areas. A panel of experts from both societies identified the main questions to be answered and developed recommendations based on the scientific evidence available at the time. The document was reviewed by the members from both societies for final approval.

Molecular method for the characterization of Coxiella burnetii from clinical and environmental samples: variability of genotypes in Spain.

BACKGROUND: Coxiella burnetii is a highly clonal microorganism which is difficult to culture, requiring BSL3 conditions for its propagation. This leads to a scarce availability of isolates worldwide. On the other hand, published methods of characterization have delineated up to 8 different genomic groups and 36 genotypes. However, all these methodologies, with the exception of one that exhibited limited discriminatory power (3 genotypes), rely on performing between 10 and 20 PCR amplifications or sequencing long fragments of DNA, which make their direct application to clinical samples impracticable and leads to a scarce accessibility of data on the circulation of C. burnetii genotypes. RESULTS: To assess the variability of this organism in Spain, we have developed a novel method that consists of a multiplex (8 targets) PCR and hybridization with specific probes that reproduce the previous classification of this organism into 8 genomic groups, and up to 16 genotypes. It allows for a direct characterization from clinical and environmental samples in a single run, which will help in the study of the different genotypes circulating in wild and domestic cycles as well as from sporadic human cases and outbreaks. The method has been validated with reference isolates. A high variability of C. burnetii has been found in Spain among 90 samples tested, detecting 10 different genotypes, being those adaA negative associated with acute Q fever cases presenting as fever of intermediate duration with liver involvement and with chronic cases. Genotypes infecting humans are also found in sheep, goats, rats, wild boar and ticks, and the only genotype found in cattle has never been found among our clinical samples. CONCLUSIONS: This newly developed methodology has permitted to demonstrate that C. burnetii is highly variable in Spain. With the data presented here, cattle seem not to participate in the transmission of C. burnetii to humans in the samples studied, while sheep, goats, wild boar, rats and ticks share genotypes with the human population.

Monkeypox and HIV in the Canary Islands: A Different Pattern in a Mobile Population.

BACKGROUND: The clinical and epidemiological data of the recent outbreak of monkeypox (MPX) differ from previous reports. One difference is the epidemiological profile; the disease mainly affects a subgroup of MSM (men who have sex with men) with high-risk sexual behaviors, frequently persons living with human immunodeficiency virus (PLHIV). METHODS: In this observational analysis, all patients with PCR (polymerase chain reaction)-confirmed MPX attending an Infectious Diseases and Tropical Medicine Unit in Gran Canaria (Spain) between May and July 2022 were considered. RESULTS: In total, 42 men were included; 88% were identified as MSM, with a median age of 40 years. Only 43% were born in Spain. All the patients had systemic symptoms and skin lesions. The distribution of lesions was more frequent in the genital/anal region, and the involvement of hands and feet was less common. Fever and lymphadenopathies were less frequent than in other series. Other unusual manifestations were proctitis, pharyngitis and penile-scrotal edema. Half of the patients had other associated infections (mainly STIs, sexually transmitted infections), and 60% of the monkeypox patients had PLHIV (People Living with HIV). When comparing the clinical characteristics between HIV-positive and -negative patients, we found three main differences: (i) a higher frequency of perioral lesions, (ii) a higher frequency of pharyngitis and (iii) a higher number of sexually transmitted infections in HIV-positive patients. CONCLUSIONS: The clinical findings in this outbreak of MPX had great variability in presentation. Several clinical differences were found in PLHIV-coinfected patients.

Detection and discrimination of Loa loa, Mansonella perstans and Wuchereria bancrofti by PCR-RFLP and nested-PCR of ribosomal DNA ITS1 region.

The ribosomal deoxyribonucleic acid (DNA) internal transcribed spacer region (ITS1) of two filarial nematodes, Loa loa and Mansonella perstans, was amplified and further sequenced to develop an species-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol for the differentiation of both species from Wuchereria bancrofti, three filarial nematodes with blood circulating microfilariae. The ITS1-PCR product digested with the restriction endonuclease Ase I generated an specific diagnostic pattern for each of the three species. Moreover, three new specific nested-PCRs, targeting the ITS1 region, for differential detection of L. loa, M. perstans and W. bancrofti were developed and used when the ITS1-PCR products were insufficient for the Ase I enzymatic digestion. These filarial species-specific molecular protocols were evaluated in forty blood samples from African adult immigrants attending in the Hospital Insular of Gran Canaria, Canarias, Spain.