Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

Background

Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger.

Methods

Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission.

Results

Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses.

Conclusions

These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data.     

AIDS and antibodies to human immunodeficiency virus (HIV) in children and their families: clinical experience at Yale-New Haven Hospital

As of December 1986, we have identified 23 symptomatic children with human immunodeficiency virus (HIV) infection in New Haven. Twelve developed AIDS as manifested by lymphocytic interstitial pneumonitis, Pneumocystis carinii pneumonia (PCP), and/or disseminated mycobacterial infections; seven of them have died. The remainder have milder clinical syndromes, which include failure to thrive, diffuse lymphadenopathy, and parotid swelling. When compared to adults with AIDS, children often have hypergammaglobulinemia and normal numbers of T4 lymphocytes. Intravenous drug abuse by the mother or mother's consort is the risk factor in 87 percent of these children. Two families have now been identified with more than one symptomatic child, but in no family is there evidence of spread from symptomatic children to uninfected siblings. A prospective study was begun to attempt to assess the risk of developing symptomatic HIV infection when a child is born to a mother with antibodies to HIV.     

Vertically transmitted HIV infection in the British Isles.

OBJECTIVE--To describe the epidemiology of vertically acquired HIV infection in the British Isles, the level of underreporting, the vertical transmission rate, and clinical spectrum of paediatric AIDS. DESIGN--Confidential, linked registers based on reporting from obstetricians and paediatricians; anonymous unlinked neonatal HIV serosurveys. SETTING--British Isles. SUBJECTS--Children born to mothers with HIV infection. MAIN OUTCOME MEASURES--Trends in HIV infection and vertical transmission rate. RESULTS--In Scotland and the Irish Republic, where most maternal HIV infection is related to drug misuse, the annual number of reports of children born to infected mothers has fallen since 1989. In England and Wales nearly half of maternal infections have been acquired overseas, and the number of children born to these women, and to women who became infected in Britain, is increasing. In south east England the proportion of live births to women whose infection was identified before delivery was only 17% (50/287), compared with 68% (26/38) in Scotland. The vertical transmission rate was 13.7% (23/168), and 23% of infected children developed AIDS in the first year of life. 41% (38/92) of children born to infected mothers who were ascertained after delivery were breast fed, compared with 5% (12/236) of those ascertained before delivery. CONCLUSIONS--The incidence of vertically transmitted HIV infection is increasing in England and Wales. More extensive antenatal testing would enable infected women to be counselled against breast feeding, which could prevent a substantial proportion of vertical transmission in some areas, and would increase opportunities for early diagnosis and treatment of infected children.     

Hyperviscosity in HIV infected children--a potential hazard during intravenous immunoglobulin therapy

A four year old boy with symptoms of HIV infection and serum IgG of 53.2 g/l had been treated for 16 months with regular infusions of intravenous immunoglobulin (IV IgG). During one such infusion he developed temporary neurological symptoms and signs suggestive of the hyperviscosity syndrome. Serum relative viscosity was raised at 5.0 (normal range 0.42-2.78). Subsequent IV IgG infusions given at a slower rate have been without adverse reactions. In a study of eight HIV infected children including the index case, and 20 children not infected with HIV, serum relative viscosity was significantly raised in the HIV infected children (p less than 0.01; students t-test). Viscosity correlated with total serum IgG, which was raised in all HIV infected children, and with serum IgM. In HIV infected children with very high levels of serum IgG a slow rate of IV IgG infusion should therefore be chosen due to the possibility of hyperviscosity.     

Hypoxaemia in young Kenyan children with acute lower respiratory infection.

OBJECTIVES--To determine the prevalence, clinical correlates, and outcome of hypoxaemia in acutely ill children with respiratory symptoms. DESIGN--Prospective observational study. SETTING--Paediatric casualty ward of a referral hospital at 1670 m altitude in Nairobi, Kenya. SUBJECTS--256 Infants and children under 3 years of age with symptoms of respiratory infection. MAIN OUTCOME MEASURES--Prevalence of hypoxaemia, defined as arterial oxygen saturation < 90% determined by pulse oximetry, and condition of patient on the fifth day after admission. RESULTS--Over half (151) of the children were hypoxaemic, and short term mortality was 4.3 times greater in these children. In contrast, the relative risk of a fatal outcome in children with radiographic pneumonia was only 1.03 times that of children without radiographic pneumonia. A logistic regression model showed that in 3-11 month old infants a respiratory rate > or = 70/min, grunting, and retractions were the best independent clinical signs for the prediction of hypoxaemia. In the older children a respiratory rate of > or = 60/min was the single best clinical predictor of hypoxaemia. The presence of hypoxaemia predicted radiographic pneumonia with a sensitivity of 71% and specificity of 55%. CONCLUSIONS--Over half the children presenting to this referral hospital with respiratory symptoms were hypoxaemic. A group of specific clinical signs seem useful in predicting hypoxaemia. The clear association of hypoxaemia with mortality suggests that the detection and effective treatment of hypoxaemia are important aspects of the clinical management of acute infections of the lower respiratory tract in children in hospital in developing regions.     

Correction of immunity disorders, treatment of intestinal infections and disbiosis in children (clinical review)

Acute viral and bacterial intestinal infections in children provoke the Tn2 immune response, resulting in development of severe and complicated forms of the disease and sustained by the disbiotic disturbances due to unnecessarily prolonged use of antibacterial drugs. Cycloferon, an early inductor of interferon-1 and -2, was shown to be safe and efficient in the complex therapy of the intestinal infections. It promoted generation of the Th2 immune response and decrease of the repeated isolation of the pathogen with normalization of the disease clinical signs. The host intestinal microflora was normalized and the level of the opportunistic organisms decreased.     

A missing piece in the puzzle: HIV in mature adults in sub-Saharan Africa

Healthcare and social needs for mature adults aged 50 years or older differ from those of younger adults due to stigma concerning HIV in older people, beliefs that engagement in sexual activity no longer applies, age driven comorbidities and responses to antiretroviral treatment, which complicate HIV diagnosis and management. In the face of a growing HIV epidemic in mature adults, mostly due to infected people aging with HIV, but also due to new infections in this age group, HIV services, which mostly cater for HIV in young adults and children, and HIV education messages and interventions, which mainly target young adults, leave the mature adult exposed and vulnerable to HIV transmission and to a lack of care and treatment thereafter.     

Poliovirus excretion in Guatemalan adults and children with HIV infection and children with cancer.

More than 20 patients with persistent poliovirus infections have been identified and reported to WHO. To date, almost all of these patients have had B-cell immune deficiency disorders. Since there are limited data on patients with HIV infection who have received oral poliovirus vaccine (OPV), we studied adults and children to determine if persons with acquired immunodeficiency due to HIV infection or cancer chemotherapy in a developing country setting had prolonged excretion of polioviruses. Stool samples from 94 HIV-infected children and 101 adults and 50 children surviving cancer in Guatemala City were cultured for polioviruses. No polioviruses were detected in any of the 195 persons with HIV infection or the 50 with cancer. The evidence from this and other studies indicates that the persistent poliovirus excretion in HIV-infected individuals is an unlikely event.     

Safety and Efficacy of Co-Trimoxazole for Treatment and Prevention of Plasmodium falciparum Malaria: A Systematic Review

Introduction

Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group.

Objective

We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis.

Result

CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%–97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%–97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%–99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women.

Conclusion

CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups.     

Disease in children infected with HIV in Abidjan,C?te d'Ivoire.

OBJECTIVE--To document the range of disease in African children infected with HIV. DESIGN--Necropsy results in consecutive children aged 1 month or more who were HIV positive and in children who were HIV negative for comparison; IgA western blots on serum samples from children under 2 years of age who were positive for HIV-1 to test the validity of routine HIV serology. SETTING--Largest hospital in Abidjan, Côte d''Ivoire. SUBJECTS--78 children who were HIV positive and 77 children who were HIV negative on whom a necropsy was performed; their median ages at death were 18 and 21 months respectively. 36 HIV positive children and 29 HIV negative children were 1-14 months old; 42 HIV positive and 48 HIV negative children were > or = 15 months old. MAIN OUTCOME MEASURES--Cause of death and prevalence of diseases confirmed pathologically. RESULTS--Respiratory tract infections were more common in HIV positive than in HIV negative children (73 (94%) v 52 (68%); P < 0.05), and were aetiologically heterogeneous. Pneumocystis carinii pneumonia was found in 11 out of 36 (31%) HIV positive children aged < 15 months, but in no HIV negative children. Among older children measles was more common in HIV positive children (8/42 (19%) v 2/48 (4%); P < 0.06). Pyogenic meningitis was present in similar proportions of HIV positive and HIV negative children aged < 15 months (7/36 (19%) and 7/29 (24%)). In HIV positive children tuberculosis (1/78), lymphocytic interstitial pneumonitis (1/78), and HIV encephalitis (2/78) were rare. CONCLUSIONS--There is greater overlap between diseases associated with HIV infection and other common health problems in African children than there is in adults. Compared with adults, HIV positive children had a high prevalence of P carinii pneumonia and a low prevalence of tuberculosis. Measles, but not malaria, was associated with HIV infection.     

Clinical signs of visceral leishmaniasis in adults: is the manner of presentation changing?

Although the typical clinical signs and symptoms of visceral leishmaniasis (VL) are always the same, in the recent years the disease has emerged in new settings, for example in HIV infected individuals, in organ transplant recipients, in patients with chronic liver disease, in pregnancy. At the same time, VL has emerged as a model for exploring the host-parasite interplay for intracellular infections. The common feature of VL is that it is fatal without treatment. Liposomal Amphotericin B is the first line treatment in developed countries. Unfortunately, the high cost makes this treatment unaffordable for developing countries.     

Potential initiators of HIV-related stigmatization: ethical and programmatic challenges for PMTCT programs

HIV/AIDS continues to constitute a serious threat to the social and physical wellbeing of African mothers and their babies. In the hardest hit countries of sub-Saharan Africa, more than 60% of all new HIV infections are occurring in women, infants and young children.Mother-to-child transmission (MTCT) constitutes 90% of new HIV infections among infants and young children. Most of these infection scan be prevented. However, the social stigma of HIV/AIDS insidiously continues to undermine the success of prevention programs.Ironically, some attributes or characteristics of prevention of mother-to-child transmission (PMTCT) programs may in fact serve as catalysts to the stigmatization process. This paper identifies and discusses six potential initiators: (1) Routine HIV testing, (2) Six months exclusive breastfeeding, (3) Incentives, (4) Home visits, (5) Location of PMTCT program, and (6) PMTCT terminology. In all these areas, there are practical strategies that may be applied to reduce the chances of being stigmatized. These strategies are introduced and discussed.     

Children, adolescents and HIV infection

The analysis of the occurrence of HIV infection in adults, children and adolescents under 18 years of age on the basis of statistical data by February 1, 1997, is presented. The total number HIV-infected persons registered by this date was 6,232; among them 902 (14.5%) were children and adolescents. 267 children were infected in the hospital focus of HIV infection; of these, 80 children (30%) died of AIDS during the period of 1989-1997. In 1992 only 16 adolescents, HIV infected were registered, while in 1995 the number of HIV-infected adolescents was 34, in 1996 their number rose to 144 and in 1997, to 435. The main cause of adolescent infections (80%) was the intravenous injection of narcotic drugs.     

May preclinical markers of brain infection by HIV be detected? A cognitive, CSF and neuroradiological investigation

A group of patients with HIV infection in various stages of the disease was studied with regard to CSF, neuroradiological and neuropsychological aspects. A considerable number of them showed signs of CNS involvement, as revealed by abnormalities in all the three fields investigated, despite a frequently unremarkable neurological examination. The findings of CSF alterations, neuroradiological abnormalities and selective cognitive impairment in the absence of opportunistic infections of the CNS support the hypothesis of an early and direct action of HIV on the nervous system.     

2-methylbutyryl-CoA dehydrogenase deficiency associated with autism and mental retardation: a case report

Pulmonary emphysema and bronchiectasis in HIV seropositive patients has been described in the presence of injection drug use, malnutrition, repeated opportunistic infections, such as Pneumocytis jirovici pneumonia and Mycobacterium tuberculosis infection, and has been linked to the presence of HIV virus in lung tissue. Given the high burden of pulmonary infections and malnutrition among people living with HIV in resource poor settings, these individuals may be at increased risk of developing pulmonary emphysema, potentially reducing the long term benefit of antiretroviral therapy (ART) if initiated late in the course of HIV infection. In this report, we describe three HIV-infected individuals (one woman and two children) presenting with extensive pulmonary cystic disease.     

Aetiology of Acute Febrile Episodes in Children Attending Korogwe District Hospital in North-Eastern Tanzania

Introduction

Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH).

Methods

A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was performed in selected cases to test for bacterial infection and a chest radiograph was requested if pneumonia was suspected. Diagnosis was based on both clinical and laboratory investigations.

Results

A total of 867 patients with a median age of 15.1 months (Interquartile range 8.6–29.9) were enrolled from January 2013 to October 2013. Respiratory tract infections were the leading clinical diagnosis with 406/867 (46.8%) of patients diagnosed with upper respiratory tract infection and 130/867 (15.0%) with pneumonia. Gastroenteritis was diagnosed in 184/867 (21.2%) of patients. Malaria infection was confirmed in 72/867 (8.3%) of patients. Bacterial infection in blood and urine accounted for 26/808 (3.2%) infections in the former, and 66/373 (17.7%) infections in the latter. HIV infection was confirmed in 10/824 (1.2%) of patients. Respiratory tract infections and gastroenteritis were frequent in patients under 36 months of age (87.3% and 91.3% respectively). Co-infections were seen in 221/867 (25.5%) of patients. The cause of fever was not identified in 65/867 (7.5%) of these patients.

Conclusions

The different proportions of infections found among febrile children reflect the causes of fever in the study area. These findings indicate the need to optimise patient management by developing malaria and non-malaria febrile illnesses management protocols.     

Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4+ cell depletion in Macaca nemestrina

With few exceptions, humans are the only species known to develop acquired immunodeficiency syndrome (AIDS) after human immunodeficiency virus (HIV) infection. We report here that an isolate of HIV type 2, EHO, readily established persistent infection in 100% of Macaca nemestrina in three consecutive transmission studies. Of the eight infected animals, five showed persistently high virus load and six developed AIDS-like diseases or CD4+ cell depletion within 4 years of infection. The pathology and clinical signs closely parallel those of HIV-1 infection of humans, including lymphadenopathy, anemia, CD4+ cell depletion, and opportunistic infections. A cell-free virus stock was established from the lymph nodes of an animal that developed AIDS-like diseases. This virus, HIV-2/287, was highly pathogenic in M. nemestrina, causing CD4+ cell depletion within 2-8 weeks postinfection. While both HIV-2 EHO and HIV-2/287 use predominantly CXCR4, the latter shows greatly enhanced replicative capacity in macaque peripheral blood mononuclear cells (PBMCs). The establishment of a human immunodeficiency virus that causes rapid and reproducible CD4 cell depletion in macaques could facilitate the study of HIV pathogenesis and the development of effective vaccines and therapy against AIDS.     

Estimated HIV Trends and Program Effects in Botswana

Background

This study uses surveillance, survey and program data to estimate past trends and current levels of HIV in Botswana and the effects of treatment and prevention programs.

Methods/Principal Findings

Data from sentinel surveillance at antenatal clinics and a national population survey were used to estimate the trend of adult HIV prevalence from 1980 to 2007. Using the prevalence trend we estimated the number of new adult infections, the transmission from mothers to children, the need for treatment and the effects of antiretroviral therapy (ART) and adult and child deaths. Prevalence has declined slowly in urban areas since 2000 and has remained stable in rural areas. National prevalence is estimated at 26% (25–27%) in 2007. About 330,000 (318,000–335,000) people are infected with HIV including 20,000 children. The number of new adult infections has been stable for several years at about 20,000 annually (12,000–26,000). The number of new child infections has declined from 4600 in 1999 to about 890 (810–980) today due to nearly complete coverage of an effective program to prevent mother-to-child transmission (PMTCT). The annual number of adult deaths has declined from a peak of over 15,500 in 2003 to under 7400 (5000–11,000) today due to coverage of ART that reaches over 80% in need. The need for ART will increase by 60% by 2016.

Conclusions

Botswana''s PMTCT and treatment programs have achieved significant results in preventing new child infections and deaths among adults and children. The number of new adult infections continues at a high level. More effective prevention efforts are urgently needed.