During the 1995 outbreak of Ebola hemorrhagic fever in the Democratic Republic of the Congo, a series of 103 cases (one-third of the total number of cases) had clinical symptoms and signs accurately recorded by medical workers, mainly in the setting of the urban hospital in Kikwit. Clinical diagnosis was confirmed retrospectively in cases for which serum samples were available (n = 63, 61% of the cases). The disease began unspecifically with fever, asthenia, diarrhea, headaches, myalgia, arthralgia, vomiting, and abdominal pain. Early inconsistent signs and symptoms included conjunctival injection, sore throat, and rash. Overall, bleeding signs were observed in <45% of the cases. Typically, terminally ill patients presented with obtundation, anuria, shock, tachypnea, and normothermia. Late manifestations, most frequently arthralgia and ocular diseases, occurred in convalescent patients. This series is the most extensive number of cases of Ebola hemorrhagic fever observed during an outbreak.

The addition of the hepatitis delta virus genomic ribozyme to the 3' end sequence of a Sendai virus defective interfering RNA (DI-H4) allowed the reproducible and efficient replication of this RNA by the viral functions expressed from cloned genes when the DI RNA was synthesized from plasmid. Limited nucleotide additions or deletions (+7 to-7 nucleotides) in the DI RNA sequence were then made at five different sites, and the different RNA derivatives were tested for their abilities to replicate. Efficient replication was observed only when the total nucleotide number was conserved, regardless of the modifications, or when the addition of a total of 6 nucleotides was made. The replicated RNAs were shown to be properly enveloped into virus particles. It is concluded that, to form a proper template for efficient replication, the Sendai virus RNA must contain a total number of nucleotides which is a multiple of 6. This was interpreted as the need for the nucleocapsid protein to contact exactly 6 nucleotides.

We have recovered infectious Sendai virus (SeV) from full‐length cDNA (FL‐3) by transfecting this cDNA and pGEM plasmids expressing the nucleocapsid protein (NP), phosphoprotein and large proteins into cells infected with a vaccinia virus which expresses T7 RNA polymerase. These cells were then injected into chicken eggs, in which SeV grows to very high titers. FL‐3 was marked with a BglII site in the leader region and an NsiI site (ATGCAT) in the 5′ nontranslated region of the NP gene, creating a new, out‐of‐frame, 5′ proximal AUG. All the virus stocks generated eventually removed this impediment to NP expression, by either point mutation or recombination between FL‐3 and pGEM‐NP. The recovery system was found to be highly recombinogenic. Even in the absence of selective pressure, one in 20 of the recombinant SeV generated had exchanged the NP gene of FL‐3 with that of pGEM‐NP. When a fifth plasmid containing a new genomic 3′ end without the presumably deleterious BglII site was included as another target for recombination, the new genomic 3′ end was found in the recombinant SeV in 12 out of 12 recoveries. Using this approach, a novel copy‐back nondefective virus was generated which interferes with wild‐type virus replication.

Laboratory diagnosis of Ebola hemorrhagic fever (EHF) is currently performed by virus isolation and serology and can be done only in a few high-containment laboratories worldwide. In 1995, during the EHF outbreak in the Democratic Republic of Congo, the possibility of using immunohistochemistry (IHC) testing of formalin-fixed postmortem skin specimens was investigated as an alternative diagnostic method for EHF. Fourteen of 19 cases of suspected EHF met the surveillance definition for EHF and were positive by IHC. IHC, serologic, and virus isolation results were concordant for all EHF and non-EHF cases. IHC and electron microscopic examination showed that endothelial cells, mononuclear phagocytes, and hepatocytes are main targets of infection, and IHC showed an association of cellular damage with viral infection. The finding of abundant viral antigens and particles in the skin of EHF patients suggests an epidemiologic role for contact transmission. IHC testing of formalin-fixed skin specimens is a safe, sensitive, and specific method for laboratory diagnosis of EHF and should be useful for EHF surveillance and prevention.

In contrast with procedures in previous Ebola outbreaks, patient care during the 1995 outbreak in Kikwit, Democratic Republic of the Congo, was centralized for a large number of patients. On 4 May, before the diagnosis of Ebola hemorrhagic fever (EHF) was confirmed by the Centers for Disease Control and Prevention, an isolation ward was created at Kikwit General Hospital. On 11 May, an international scientific and technical committee established as a priority the improvement of hygienic conditions in the hospital and the protection of health care workers and family members; to this end, protective equipment was distributed and barrier-nursing techniques were implemented. For patients living far from Kikwit, home care was organized. Initially, hospitalized patients were given only oral treatments; however, toward the end of the epidemic, infusions and better nutritional support were given, and 8 patients received blood from convalescent EHF patients. Only 1 of the transfusion patients died (12.5%). It is expected that with improved medical care, the case fatality rate of EHF could be reduced.

A natural Sendai virus internal deletion defective interfering (DI) RNA, previously shown to encode a truncated NP protein and previously cloned under the control of the T7 RNA polymerase promoter, was expressed from plasmid and shown to replicate in cell tissue culture when the viral proteins NP, P, and L were coexpressed from cloned genes. The efficient replication was dependent on the total length of the RNA to be a multiple of 6 nucleotides, showing that the "rule of six" applied for a DI RNA that has conserved the end sequences of the nondefective viral RNA. Compared to the copy-back H4 DI RNA, the replication efficiency of the internal deletion DI RNA was reproducibly 20-fold lower. Reciprocal exchanges between the minus-strand 3'-end primary sequences of the two DI RNAs showed that the replication efficiency of the derivatives obtained directly correlated with the origin and the extent of the primary sequence. Moreover, some of the derivatives exhibited a replication efficiency comparable to that of the copy-back DI RNA with, however, the ability to transcribe a functional mRNA similar to the internal deletion DI RNA. This indicated that the transcription ability of a viral RNA was not sufficient to explain a low replication efficiency.

One third of previously treated patients had MDR TB.

It is generally assumed by the donor community that the targeted funding of global, regional or cross-border surveillance programmes is an efficient way to support resource-poor countries in developing their own national public health surveillance infrastructure, to encourage national authorities to share outbreak intelligence, and ultimately to ensure compliance of World Health Organization (WHO) Member States with the revised (2005) International Health Regulations. At country level, a number of factors and constraints appear to contradict this view. Global or regional surveillance initiatives, including syndromic surveillance and rumour surveillance projects, have been conceived in neglect of fragile health systems, from which they extract scarce human resources. In contradiction with a rightful stance promoting 'integrated surveillance' by WHO, the nurturing of donor-driven, poorly coordinated and redundant surveillance networks generally adds further fragmentation to national health priorities set up by developing countries. In their current categorical format, ignoring the overwhelming deficits in governance and health care capacity, global surveillance strategies seem bound to benefit mainly the most industrially developed nations through the provision of early warning information or scientific data. In lower-income countries, a focus of resources on strengthening the health system first would ultimately be a more efficient way to achieve proper detection and response to outbreaks at national or sub-national level. As documented in several pilot initiatives at sub-national level (India, South Africa, Tuvalu and Cambodia), the empowerment of frontline health workers and communities is a key element for an efficient surveillance system. Such simple measures centred on human resources and community values appear to be more beneficial than massive and conditional monetary inputs.